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12 - Apoptosis and chemoresistance

from Part II - Cell biology and pathobiology

Published online by Cambridge University Press:  01 July 2010

By
Kirsteen H. Maclean  and
John L. Cleveland
Edited by
Ching-Hon Pui
Kirsteen H. Maclean
Affiliation:
Research Fellow, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA
John L. Cleveland
Affiliation:
Member, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA
Ching-Hon Pui
Affiliation:
St. Jude Children's Research Hospital, Memphis
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Summary

Introduction

The development of chemoresistance in tumors is a major obstacle in oncology, particularly in the treatment of acute myeloid leukemia. Resistance to therapy can be broad (multidrug resistance) and arise de novo, but is more frequently acquired following the relapse of disease in patients previously treated with chemotherapy. The chemoresistance phenotype can arise through several mechanisms including: (1) overexpression of the P-glycoprotein family of membrane transporters (MDR1, MRP, LRP), which decrease the intracellular levels of anticancer drugs; (2) changes in cellular enzymes that detoxify or metabolize drugs, such as dihydrofolate reductase and cytochrome p450 enzymes; and (3) changes in enzymes intimately involved in DNA repair, such as DNA topoisomerase II. A fourth and more general mechanism involves changes in the expression and/or activity of proteins that regulate apoptosis, an endogenous program of cell suicide that disassembles the cell when it has received damage or oncogenic insults. Given the number of regulators that feed into the apoptotic response, understanding this mechanism of resistance is now recognized as a significant challenge; however, targeting these regulators holds great promise of overcoming or bypassing drug resistance in relapsed cancer patients.

For many years, radiation treatment and chemotherapy were thought to cause irreparable metabolic or physical damage to cancer cells, resulting in cell necrosis.

Type
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Information
Childhood Leukemias , pp. 339 - 361
Publisher: Cambridge University Press
Print publication year: 2006

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References

Noskova, V., Dzubak, P., Kuzmina, G., et al.In vitro chemoresistance profile and expression/function of MDR associated proteins in resistant cell lines derived from CCRF-CEM, K562, A549 and MDA MB 231 parental cells. Neoplasma, 2002; 49: 418–25.Google Scholar
Bodo, A., Bakos, E., Szeri, F., Varadi, A., & Sarkadi, B.The role of multidrug transporters in drug availability, metabolism and toxicity. Toxicol Lett, 2003; 140–141: 133–43.CrossRefGoogle ScholarPubMed
Ribrag, V., Massaad, L., Janot, F., et al.Main drug-metabolizing enzyme systems in human non-Hodgkin's lymphomas sensitive or resistant to chemotherapy. Leuk Lymphoma, 1995; 18: 303–10.CrossRefGoogle ScholarPubMed
Yasui, K., Mihara, S., Zhao, C., et al.Alteration in copy numbers of genes as a mechanism for acquired drug resistance. Cancer Res, 2004; 64: 1403–10.CrossRefGoogle ScholarPubMed
Galmarini, C. M.P-glycoprotein expression by cancer cells affects cell cytotoxicity and cell-cycle perturbations induced by six chemotherapeutic drugs. J Exp Ther Oncol, 2002; 2: 146–52.CrossRefGoogle ScholarPubMed
Galmarini, C. M., Thomas, X., Calvo, F., et al.In vivo mechanisms of resistance to cytarabine in acute myeloid leukaemia. Br J Haematol, 2002; 117: 860–8.CrossRefGoogle ScholarPubMed
Fadok, V. A., Savill, J. S., Haslett, C., et al.Different populations of macrophages use either the vitronectin receptor or the phosphatidylserine receptor to recognize and remove apoptotic cells. J Immunol, 1992; 149: 4029–35.Google ScholarPubMed
Cohen, J. J., Duke, R. C., Fadok, V. A., & Sellins, K. S.Apoptosis and programmed cell death in immunity. Annu Rev Immunol, 1992; 10: 267–93.CrossRefGoogle ScholarPubMed
Parker, J. E. & Mufti, G. J.The myelodysplastic syndromes: a matter of life or death. Acta Haematol, 2004; 111: 78–99.CrossRefGoogle ScholarPubMed
Stein, S. M. & Dale, D. C.Molecular basis and therapy of disorders associated with chronic neutropenia. Curr Allergy Asthma Rep, 2003; 3: 385–8.CrossRefGoogle ScholarPubMed
Braess, J., Schneiderat, P., Schoch, C., et al.Functional analysis of apoptosis induction in acute myeloid leukaemia: relevance of karyotype and clinical treatment response. Br J Haematol, 2004; 126: 338–47.CrossRefGoogle ScholarPubMed
Green, D. R. & Kroemer, G.The pathophysiology of mitochondrial cell death. Science, 2004; 305: 626–9.CrossRefGoogle ScholarPubMed
Debatin, K. M. & Krammer, P. H.Death receptors in chemotherapy and cancer. Oncogene, 2004; 23: 2950–66.CrossRefGoogle ScholarPubMed
Catalfamo, M. & Henkart, P. A.Perforin and the granule exocytosis cytotoxicity pathway. Curr Opin Immunol, 2003; 15: 522–7.CrossRefGoogle ScholarPubMed
Raja, S. M., Wang, B., Dantuluri, M., et al.Cytotoxic cell granule-mediated apoptosis. Characterization of the macromolecular complex of granzyme B with serglycin. J Biol Chem, 2002; 277: 49 523–30.CrossRefGoogle ScholarPubMed
Thornberry, N. A. & Lazebnik, Y.Caspases: enemies within. Science, 1998; 281: 1312–16.CrossRefGoogle Scholar
Martinon, F. & Tschopp, J.Inflammatory caspases: linking an intracellular innate immune system to autoinflammatory diseases. Cell, 2004; 117: 561–74.CrossRefGoogle ScholarPubMed
Shi, Y.Caspase activation: revisiting the induced proximity model. Cell, 2004; 117: 855–8.CrossRefGoogle ScholarPubMed
Wyllie, A. H., Kerr, J. F. & Currie, A. R.Cell death: the significance of apoptosis. Int Rev Cytol, 1980; 68: 251–306.CrossRefGoogle Scholar
Enari, M., Sakahira, H., Yokoyama, H., et al.A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD. Nature 1998; 391: 43–50.CrossRefGoogle ScholarPubMed
Nicholson, D. W., Ali, A., Thornberry, N. A., et al.Identification and inhibition of the ICE/CED-3 protease necessary for mammalian apoptosis. Nature, 1995; 376: 37–43.CrossRefGoogle ScholarPubMed
Fischer, U., Janicke, R. U., & Schulze-Osthoff, K.Many cuts to ruin: a comprehensive update of caspase substrates. Cell Death Differ, 2003; 10: 76–100.CrossRefGoogle ScholarPubMed
Harada, K., Toyooka, S., Shivapurkar, N., et al.Deregulation of caspase 8 and 10 expression in pediatric tumors and cell lines. Cancer Res, 2002; 62: 5897–901.Google ScholarPubMed
Trojan, J., Brieger, A., Raedle, J., et al.BAX and caspase-5 frameshift mutations and spontaneous apoptosis in colorectal cancer with microsatellite instability. Int J Colorectal Dis, 2004; 19: 538–44.CrossRefGoogle ScholarPubMed
Soung, Y. H., Lee, J. W., Kim, H. S., et al.Inactivating mutations of CASPASE-7 gene in human cancers. Oncogene, 2003; 22: 8048–52.CrossRefGoogle ScholarPubMed
Baylin, S. & Bestor, T. H.Altered methylation patterns in cancer cell genomes: cause or consequence ?Cancer Cell, 2002; 1: 299–305.CrossRefGoogle ScholarPubMed
Teitz, T., Wei, T., Valentine, M. B., et al.Caspase 8 is deleted or silenced preferentially in childhood neuroblastomas with amplification of MYCN. Nat Med, 2000; 6: 529–35.CrossRefGoogle ScholarPubMed
Fulda, S., Kufer, M. U., Meyer, E., et al.Sensitization for death receptor- or drug-induced apoptosis by re-expression of caspase-8 through demethylation or gene transfer. Oncogene, 2001; 20: 5865–77.CrossRefGoogle ScholarPubMed
Yu, J., Ni, M., Xu, J., et al.Methylation profiling of twenty promoter-CpG islands of genes which may contribute to hepatocellular carcinogenesis. BMC Cancer, 2002; 2: 29.CrossRefGoogle ScholarPubMed
Worm, J. & Guldberg, P.DNA methylation: an epigenetic pathway to cancer and a promising target for anticancer therapy. J Oral Pathol Med, 2002; 31: 443–9.CrossRefGoogle Scholar
Roman-Gomez, J., Castillejo, J. A., Jimenez, A., et al.The role of DNA hypermethylation in the pathogenesis and prognosis of acute lymphoblastic leukemia. Leuk Lymphoma, 2003; 44: 1855–64.CrossRefGoogle ScholarPubMed
Soengas, M. S., Alarcon, R. M., Yoshida, H., et al.Apaf-1 and caspase-9 in p53-dependent apoptosis and tumor inhibition. Science, 1999; 284: 156–9.CrossRefGoogle ScholarPubMed
Marsden, V. S., O'Connor, L., O'Reilly, L. A., et al.Apoptosis initiated by Bcl-2-regulated caspase activation independently of the cytochrome c/Apaf-1/caspase-9 apoptosome. Nature, 2002; 419: 634–7.CrossRefGoogle ScholarPubMed
Schimmer, A. D., Pedersen, I. M., Kitada, S., et al.Functional blocks in caspase activation pathways are common in leukemia and predict patient response to induction chemotherapy. Cancer Res, 2003; 63: 1242–8.Google ScholarPubMed
Tsujimoto, Y., Cossman, J., Jaffe, E., & Croce, C. M.Involvement of the bcl-2 gene in human follicular lymphoma. Science, 1985; 228: 1440–3.CrossRefGoogle ScholarPubMed
Cleary, M. L. & Sklar, J.Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18. Proc Natl Acad Sci U S A, 1985; 82: 7439–43.CrossRefGoogle Scholar
Vaux, D. L., Cory, S., & Adams, J. M.Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature, 1988; 335: 440–2.CrossRefGoogle ScholarPubMed
Kirkin, V., Joos, S., & Zornig, M.The role of Bcl-2 family members in tumorigenesis. Biochim Biophys Acta, 2004; 1644: 229–49.CrossRefGoogle ScholarPubMed
Breckenridge, D. G., Germain, M., Mathai, J. P., Nguyen, M., & Shore, G. C.Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene, 2003; 22: 8608–18.CrossRefGoogle ScholarPubMed
Orrenius, S.Mitochondrial regulation of apoptotic cell death. Toxicol Lett, 2004; 149: 19–23.CrossRefGoogle ScholarPubMed
Scorrano, L., Oakes, S. A., Opferman, J. T., et al.BAX and BAK regulation of endoplasmic reticulum Ca2+: a control point for apoptosis. Science, 2003; 300: 135–9.CrossRefGoogle ScholarPubMed
Debatin, K. M., Poncet, D., & Kroemer, G.Chemotherapy: targeting the mitochondrial cell death pathway. Oncogene, 2002; 21: 8786–803.CrossRefGoogle ScholarPubMed
Zamzami, N., Marchetti, P., Castedo, M., et al.Reduction in mitochondrial potential constitutes an early irreversible step of programmed lymphocyte death in vivo. J Exp Med, 1995; 181: 1661–72.CrossRefGoogle ScholarPubMed
Vayssiere, J. L., Petit, P. X., Risler, Y., & Mignotte, B.Commitment to apoptosis is associated with changes in mitochondrial biogenesis and activity in cell lines conditionally immortalized with simian virus 40. Proc Natl Acad Sci U S A, 1994; 91: 11 752–6.CrossRefGoogle ScholarPubMed
Jiang, X. & Wang, X.Cytochrome c promotes caspase-9 activation by inducing nucleotide binding to Apaf-1. J Biol Chem, 2000; 275: 31 199–203.CrossRefGoogle ScholarPubMed
Susin, S. A., Lorenzo, H. K., Zamzami, N., et al.Molecular characterization of mitochondrial apoptosis-inducing factor. Nature, 1999; 397: 441–6.CrossRefGoogle ScholarPubMed
Iyer, N. G., Chin, S. F., Ozdag, H., et al.p300 regulates p53-dependent apoptosis after DNA damage in colorectal cancer cells by modulation of PUMA/p21 levels. Proc Natl Acad Sci U S A, 2004; 101: 7386–91.CrossRefGoogle ScholarPubMed
Hershko, T. & Ginsberg, D.Up-regulation of Bcl-2 homology 3 (BH3)-only proteins by E2F1 mediates apoptosis. J Biol Chem, 2004; 279: 8627–34.CrossRefGoogle ScholarPubMed
Maclean, K. H., Keller, U. B., Rodriguez-Galindo, C., Nilsson, J. A., & Cleveland, J. L.c-Myc augments gamma irradiation-induced apoptosis by suppressing Bcl-X(L). Mol Cell Biol, 2003; 23: 7256–70.CrossRefGoogle Scholar
Lotem, J. & Sachs, L.Regulation by bcl-2, c-myc, and p53 of susceptibility to induction of apoptosis by heat shock and cancer chemotherapy compounds in differentiation-competent and -defective myeloid leukemic cells. Cell Growth Differ, 1993; 4: 41–7.Google ScholarPubMed
Miyashita, T. & Reed, J. C.Bcl-2 oncoprotein blocks chemotherapy-induced apoptosis in a human leukemia cell line. Blood, 1993; 81: 151–7.Google Scholar
Walton, M. I., Whysong, D., O'Connor, P. M., et al.Constitutive expression of human Bcl-2 modulates nitrogen mustard and camptothecin induced apoptosis. Cancer Res, 1993; 53: 1853–61.Google ScholarPubMed
Sentman, C. L., Shutter, J. R., Hockenbery, D., Kanagawa, O., & Korsmeyer, S. J.bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes. Cell, 1991; 67: 879–88.CrossRefGoogle Scholar
Strasser, A., Harris, A. W., & Cory, S.bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell, 1991; 67: 889–99.CrossRefGoogle ScholarPubMed
Nunez, G., London, L., Hockenbery, D., et al.Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines. J Immunol, 1990; 144: 3602–10.Google ScholarPubMed
Adams, J. M., Harris, A. W., Pinkert, C. A., et al.The c-myc oncogene driven by immunoglobulin enhancers induces lymphoid malignancy in transgenic mice. Nature, 1985; 318: 533–8.CrossRefGoogle ScholarPubMed
Harris, A. W., Pinkert, C. A., Crawford, M., et al.The E mu-myc transgenic mouse. A model for high-incidence spontaneous lymphoma and leukemia of early B cells. J Exp Med, 1988; 167: 353–71.CrossRefGoogle Scholar
Schmitt, C. A., Wallace-Brodeur, R. R., Rosenthal, C. T., McCurrach, M. E., & Lowe, S. W.DNA damage responses and chemosensitivity in the E mu-myc mouse lymphoma model. Cold Spring Harb Symp Quant Biol, 2000; 65: 499–510.CrossRefGoogle Scholar
Kondo, S., Shinomura, Y., Miyazaki, Y., et al.Mutations of the bak gene in human gastric and colorectal cancers. Cancer Res, 2000; 60: 4328–30.Google ScholarPubMed
Sturm, I., Papadopoulos, S., Hillebrand, T., et al.Impaired BAX protein expression in breast cancer: mutational analysis of the BAX and the p53 gene. Int J Cancer, 2000; 87: 517–21.3.0.CO;2-B>CrossRefGoogle ScholarPubMed
Paoloni-Giacobino, A., Rey-Berthod, C., Couturier, A., Antonarakis, S. E., & Hutter, P.Differential rates of frameshift alterations in four repeat sequences of hereditary nonpolyposis colorectal cancer tumors. Hum Genet, 2002; 111: 284–9.CrossRefGoogle ScholarPubMed
Mrozek, A., Petrowsky, H., Sturm, I., et al.Combined p53/Bax mutation results in extremely poor prognosis in gastric carcinoma with low microsatellite instability. Cell Death Differ, 2003; 10: 461–7.CrossRefGoogle ScholarPubMed
Wani, K. M., Huilgol, N. G., Hongyo, T., et al.Genetic alterations in the coding region of the bak gene in uterine cervical carcinoma. Br J Cancer, 2003; 88: 1584–6.CrossRefGoogle ScholarPubMed
Inoue, K., Kohno, T., Takakura, S., et al.Frequent microsatellite instability and BAX mutations in T cell acute lymphoblastic leukemia cell lines. Leuk Res, 2000; 24: 255–62.CrossRefGoogle ScholarPubMed
Gaidano, G., Vivenza, D., Forconi, F., et al.Mutation of BAX occurs infrequently in acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas. Genes Chromosomes Cancer, 2000; 27: 177–82.3.0.CO;2-O>CrossRefGoogle ScholarPubMed
Ionov, Y., Yamamoto, H., Krajewski, S., Reed, J. C., & Perucho, M.Mutational inactivation of the proapoptotic gene BAX confers selective advantage during tumor clonal evolution. Proc Natl Acad Sci U S A, 2000; 97: 10 872–7.CrossRefGoogle ScholarPubMed
Bosanquet, A. G., Sturm, I., Wieder, T., et al.Bax expression correlates with cellular drug sensitivity to doxorubicin, cyclophosphamide and chlorambucil but not fludarabine, cladribine or corticosteroids in B cell chronic lymphocytic leukemia. Leukemia, 2002; 16: 1035–44.CrossRefGoogle ScholarPubMed
McCurrach, M. E., Connor, T. M., Knudson, C. M., Korsmeyer, S. J., & Lowe, S. W.bax-deficiency promotes drug resistance and oncogenic transformation by attenuating p53-dependent apoptosis. Proc Natl Acad Sci U S A, 1997; 94: 2345–9.CrossRefGoogle ScholarPubMed
LeBlanc, H., Lawrence, D., Varfolomeev, E., et al.Tumor-cell resistance to death receptor-induced apoptosis through mutational inactivation of the proapoptotic Bcl-2 homolog Bax. Nat Med, 2002; 8: 274–81.CrossRefGoogle ScholarPubMed
Wei, M. C., Zong, W. X., Cheng, E. H., et al.Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death. Science, 2001; 292: 727–30.CrossRefGoogle ScholarPubMed
Kondo, E., Yoshino, T., Yamadori, I., et al.Expression of Bcl-2 protein and Fas antigen in non-Hodgkin's lymphomas. Am J Pathol, 1994; 145: 330–7.Google ScholarPubMed
Wilson, W. H., Teruya-Feldstein, J., Fest, T., et al.Relationship of p53, bcl-2, and tumor proliferation to clinical drug resistance in non-Hodgkin's lymphomas. Blood, 1997; 89: 601–9.Google ScholarPubMed
Matolcsy, A., Warnke, R. A., & Knowles, D. M.Somatic mutations of the translocated bcl-2 gene are associated with morphologic transformation of follicular lymphoma to diffuse large-cell lymphoma. Ann Oncol, 1997; 8(Suppl. 2): 119–22.CrossRefGoogle ScholarPubMed
Ek, S., Hogerkorp, C. M., Dictor, M., Ehinger, M., & Borrebaeck, C. A.Mantle cell lymphomas express a distinct genetic signature affecting lymphocyte trafficking and growth regulation as compared with subpopulations of normal human B cells. Cancer Res, 2002; 62: 4398–405.Google ScholarPubMed
Camilleri-Broet, S., Davi, F., Feuillard, J., et al.High expression of latent membrane protein 1 of Epstein-Barr virus and BCL-2 oncoprotein in acquired immunodeficiency syndrome-related primary brain lymphomas. Blood, 1995; 86: 432–5.Google ScholarPubMed
Geelen, F. A., Vermeer, M. H., Meijer, C. J., et al.bcl-2 protein expression in primary cutaneous large B-cell lymphoma is site-related. J Clin Oncol, 1998; 16: 2080–5.CrossRefGoogle ScholarPubMed
Zaja, F., Di Loreto, C., Amoroso, V., et al.BCL-2 immunohistochemical evaluation in B-cell chronic lymphocytic leukemia and hairy cell leukemia before treatment with fludarabine and 2-chloro-deoxy-adenosine. Leuk Lymphoma, 1998; 28: 567–72.CrossRefGoogle ScholarPubMed
Cervero, C., Escribano, L., San Miguel, J. F., et al.Expression of Bcl-2 by human bone marrow mast cells and its overexpression in mast cell leukemia. Am J Hematol, 1999; 60: 191–5.3.0.CO;2-Y>CrossRefGoogle ScholarPubMed
Campana, D., Coustan-Smith, E., Manabe, A., et al.Prolonged survival of B-lineage acute lymphoblastic leukemia cells is accompanied by overexpression of bcl-2 protein. Blood, 1993; 81: 1025–31.Google ScholarPubMed
Pontvert-Delucq, S., Hibner, U., Vilmer, E., et al.Heterogen eity of B lineage acute lymphoblastic leukemias (B-ALL) with regard to their in vitro spontaneous proliferation, growth factor response and BCL-2 expression. Leuk Lymphoma, 1996; 21: 267–80.CrossRefGoogle Scholar
Gottardi, D., Alfarano, A., De Leo, A. M., et al.Defective apoptosis due to Bcl-2 overexpression may explain why B-CLL cells accumulate in G0. Curr Top Microbiol Immunol, 1995; 194: 307–12.Google ScholarPubMed
Campos, L., Rouault, J. P., Sabido, O., et al.High expression of bcl-2 protein in acute myeloid leukemia cells is associated with poor response to chemotherapy. Blood, 1993; 81: 3091–6.Google ScholarPubMed
Maung, Z. T., MacLean, F. R., Reid, M. M., et al.The relationship between bcl-2 expression and response to chemotherapy in acute leukaemia. Br J Haematol, 1994; 88: 105–9.CrossRefGoogle ScholarPubMed
Karakas, T., Maurer, U., Weidmann, E., et al.High expression of bcl-2 mRNA as a determinant of poor prognosis in acute myeloid leukemia. Ann Oncol, 1998; 9: 159–65.CrossRefGoogle ScholarPubMed
Bincoletto, C., Saad, S. T., da Silva, E. S., & Queiroz, M. L.Haematopoietic response and bcl-2 expression in patients with acute myeloid leukaemia. Eur J Haematol, 1999; 62: 38–42.CrossRefGoogle ScholarPubMed
Pallis, M., Zhu, Y. M., & Russell, N. H.Bcl-x(L) is heterogenously expressed by acute myeloblastic leukaemia cells and is associated with autonomous growth in vitro and with P-glycoprotein expression. Leukemia, 1997; 11: 945–9.CrossRefGoogle ScholarPubMed
Deng, G., Lane, C., Kornblau, S., et al.Ratio of bcl-xshort to bcl-xlong is different in good- and poor-prognosis subsets of acute myeloid leukemia. Mol Med, 1998; 4: 158–64.Google ScholarPubMed
Konopleva, M., Zhao, S., Hu, W., et al.The anti-apoptotic genes Bcl-X(L) and Bcl-2 are over-expressed and contribute to chemoresistance of non-proliferating leukaemic CD34+ cells. Br J Haematol, 2002; 118: 521–34.CrossRefGoogle ScholarPubMed
Gutierrez-Castellanos, S., Cruz, M., Rabelo, L., et al.Differences in BCL-X(L) expression and STAT5 phosphorylation in chronic myeloid leukaemia patients. Eur J Haematol, 2004; 72: 231–8.CrossRefGoogle ScholarPubMed
Garcia, J. F., Camacho, F. I., Morente, M., et al.Hodgkin and Reed-Sternberg cells harbor alterations in the major tumor suppressor pathways and cell-cycle checkpoints: analyses using tissue microarrays. Blood, 2003; 101: 681–9.CrossRefGoogle ScholarPubMed
Schlaifer, D., Krajewski, S., Galoin, S., et al.Immunodetection of apoptosis-regulating proteins in lymphomas from patients with and without human immunodeficiency virus infection. Am J Pathol, 1996; 149: 177–85.Google ScholarPubMed
Tu, Y., Renner, S., Xu, F., et al.BCL-X expression in multiple myeloma: possible indicator of chemoresistance. Cancer Res, 1998; 58: 256–62.Google ScholarPubMed
Cho-Vega, J. H., Rassidakis, G. Z., Admirand, J. H., et al.MCL-1 expression in B-cell non-Hodgkin's lymphomas. Hum Pathol, 2004; 35: 1095–100.CrossRefGoogle ScholarPubMed
Jourdan, M., Veyrune, J. L., Vos, J. D., et al.A major role for Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells. Oncogene, 2003; 22: 2950–9.CrossRefGoogle Scholar
Rassidakis, G. Z., Jones, D., Lai, R., et al.BCL-2 family proteins in peripheral T-cell lymphomas: correlation with tumour apoptosis and proliferation. J Pathol, 2003; 200: 240–8.CrossRefGoogle ScholarPubMed
Khoury, J. D., Medeiros, L. J., Rassidakis, G. Z., et al.Expression of Mcl-1 in mantle cell lymphoma is associated with high-grade morphology, a high proliferative state, and p53 overexpression. J Pathol, 2003; 199: 90–7.CrossRefGoogle ScholarPubMed
Moshynska, O., Sankaran, K., Pahwa, P., & Saxena, A.Prognostic significance of a short sequence insertion in the MCL-1 promoter in chronic lymphocytic leukemia. J Natl Cancer Inst, 2004; 96: 673–82.CrossRefGoogle Scholar
Kaufmann, S. H., Karp, J. E., Svingen, P. A., et al.Elevated expression of the apoptotic regulator Mcl-1 at the time of leukemic relapse. Blood, 1998; 91: 991–1000.Google ScholarPubMed
Moreb, J. S. & Zucali, J.Human A1 expression in acute myeloid leukemia and its relationship to Bcl-2 expression. Blood, 2001; 97: 578–9.CrossRefGoogle ScholarPubMed
McDonnell, T. J., Deane, N., Platt, F. M., et al.bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell, 1989; 57: 79–88.CrossRefGoogle ScholarPubMed
McDonnell, T. J. & Korsmeyer, S. J.Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14; 18). Nature, 1991; 349: 254–6.CrossRefGoogle Scholar
Linette, G. P., Hess, J. L., Sentman, C. L., & Korsmeyer, S. J.Peripheral T-cell lymphoma in lckpr-bcl-2 transgenic mice. Blood, 1995; 86: 1255–60.Google ScholarPubMed
Strasser, A., Harris, A. W., Bath, M. L., & Cory, S.Novel primitive lymphoid tumours induced in transgenic mice by cooperation between myc and bcl-2. Nature, 1990; 348: 331–3.CrossRefGoogle ScholarPubMed
Cheung, W. C., Kim, J. S., Linden, M., et al.Novel targeted deregulation of c-Myc cooperates with Bcl-X(L) to cause plasma cell neoplasms in mice. J Clin Invest, 2004; 113: 1763–73.CrossRefGoogle ScholarPubMed
Swanson, P. J., Kuslak, S. L., Fang, W., et al.Fatal acute lymphoblastic leukemia in mice transgenic for B cell-restricted bcl-xL and c-myc. J Immunol, 2004; 172: 6684–91.CrossRefGoogle ScholarPubMed
Kogan, S. C., Brown, D. E., Shultz, D. B., et al.BCL-2 cooperates with promyelocytic leukemia retinoic acid receptor alpha chimeric protein (PMLRARalpha) to block neutrophil differentiation and initiate acute leukemia. J Exp Med, 2001; 193: 531–43.CrossRefGoogle ScholarPubMed
Jaiswal, S., Traver, D., Miyamoto, T., et al.Expression of BCR/ABL and BCL-2 in myeloid progenitors leads to myeloid leukemias. Proc Natl Acad Sci U S A, 2003; 100: 10 002–7.CrossRefGoogle ScholarPubMed
Eischen, C. M., Woo, D., Roussel, M. F., & Cleveland, J. L.Apoptosis triggered by Myc-induced suppression of Bcl-X(L) or Bcl-2 is bypassed during lymphomagenesis. Mol Cell Biol, 2001; 21: 5063–70.CrossRefGoogle ScholarPubMed
Eischen, C. M., Roussel, M. F., Korsmeyer, S. J., & Cleveland, J. L.Bax loss impairs Myc-induced apoptosis and circumvents the selection of p53 mutations during Myc-mediated lymphomagenesis. Mol Cell Biol, 2001; 21: 7653–62.CrossRefGoogle ScholarPubMed
Marcucci, G., Stock, W., Dai, G., et al.G3139, a BCL-2 antisense oligo-nucleotide, in AML. Ann Hematol, 2004; 83(Suppl. 1) S93–4.Google ScholarPubMed
Tolcher, A. W., Kuhn, J., Schwartz, G., et al.A phase I pharmacokinetic and biological correlative study of oblimersen sodium (genasense, g3139), an antisense oligonucleotide to the bcl-2 mRNA, and of docetaxel in patients with hormone-refractory prostate cancer. Clin Cancer Res, 2004; 10: 5048–57.CrossRefGoogle Scholar
Hopkins-Donaldson, S., Cathomas, R., Simoes-Wust, A. P., et al.Induction of apoptosis and chemosensitization of mesothelioma cells by Bcl-2 and Bcl-xL antisense treatment. Int J Cancer, 2003; 106: 160–6.CrossRefGoogle ScholarPubMed
Jiang, M. & Milner, J.Bcl-2 constitutively suppresses p53-dependent apoptosis in colorectal cancer cells. Genes Dev, 2003; 17: 832–7.CrossRefGoogle ScholarPubMed
Wang, J. L., Liu, D., Zhang, Z. J., et al.Structure-based discovery of an organic compound that binds Bcl-2 protein and induces apoptosis of tumor cells. Proc Natl Acad Sci U S A, 2000; 97: 7124–9.CrossRefGoogle ScholarPubMed
Tzung, S. P., Kim, K. M., Basanez, G., et al.Antimycin A mimics a cell-death-inducing Bcl-2 homology domain 3. Nat Cell Biol, 2001; 3: 183–91.CrossRefGoogle ScholarPubMed
Vieira, H. L., Boya, P., Cohen, I., et al.Cell permeable BH3-peptides overcome the cytoprotective effect of Bcl-2 and Bcl-X(L). Oncogene, 2002; 21: 1963–77.CrossRefGoogle Scholar
Peter, M. E. & Krammer, P. H.The CD95(APO-1/Fas) DISC and beyond. Cell Death Differ, 2003; 10: 26–35.CrossRefGoogle ScholarPubMed
Idriss, H. T. & Naismith, J. H.TNF alpha and the TNF receptor superfamily: structure-function relationship(s). Microsc Res Tech, 2000; 50: 184–95.3.0.CO;2-H>CrossRefGoogle Scholar
Cleveland, J. L. & Ihle, J. N.Contenders in FasL/TNF death signaling. Cell, 1995; 81: 479–82.CrossRefGoogle ScholarPubMed
Zimmermann, K. C., Bonzon, C., & Green, D. R.The machinery of programmed cell death. Pharmacol Ther, 2001; 92: 57–70.CrossRefGoogle ScholarPubMed
Barnhart, B. C., Alappat, E. C., & Peter, M. E.The CD95 type I/type II model. Semin Immunol, 2003; 15: 185–93.CrossRefGoogle ScholarPubMed
Irmler, M., Thome, M., Hahne, M., et al.Inhibition of death receptor signals by cellular FLIP. Nature, 1997; 388: 190–5.CrossRefGoogle ScholarPubMed
LeBlanc, H. N. & Ashkenazi, A.Apo2L/TRAIL and its death and decoy receptors. Cell Death Differ, 2003; 10: 66–75.CrossRefGoogle ScholarPubMed
O'Gorman, D. M. & Cotter, T. G.Molecular signals in anti-apoptotic survival pathways. Leukemia, 2001; 15: 21–34.CrossRefGoogle ScholarPubMed
Friesen, C., Herr, I., Krammer, P. H., & Debatin, K. M.Involvement of the CD95 (APO-1/FAS) receptor/ligand system in drug-induced apoptosis in leukemia cells. Nat Med, 1996; 2: 574–7.CrossRefGoogle ScholarPubMed
Posovszky, C., Friesen, C., Herr, I., & Debatin, K. M.Chemotherapeutic drugs sensitize pre-B ALL cells for CD95- and cytotoxic T-lymphocyte-mediated apoptosis. Leukemia, 1999; 13: 400–9.CrossRefGoogle ScholarPubMed
Lam, V., Findley, H. W., Reed, J. C., Freedman, M. H., & Goldenberg, G. J.Comparison of DR5 and Fas expression levels relative to the chemosensitivity of acute lymphoblastic leukemia cell lines. Leuk Res, 2002; 26: 503–13.CrossRefGoogle ScholarPubMed
Villunger, A., Egle, A., Marschitz, I., et al.Constitutive expression of Fas (Apo-1/CD95) ligand on multiple myeloma cells: a potential mechanism of tumor-induced suppression of immune surveillance. Blood, 1997; 90: 12–20.Google ScholarPubMed
Munker, R., Lubbert, M., Yonehara, S., et al.Expression of the Fas antigen on primary human leukemia cells. Ann Hematol, 1995; 70: 15–17.CrossRefGoogle ScholarPubMed
Min, Y. J., Lee, J. H., Choi, S. J., et al.Prognostic significance of Fas (CD95) and TRAIL receptors (DR4/DR5) expression in acute myelogenous leukemia. Leuk Res, 2004; 28: 359–65.CrossRefGoogle ScholarPubMed
Lacour, S., Hammann, A., Wotawa, A., et al.Anticancer agents sensitize tumor cells to tumor necrosis factor-related apoptosis-inducing ligand-mediated caspase-8 activation and apoptosis. Cancer Res, 2001; 61: 1645–51.Google ScholarPubMed
Petak, I. & Houghton, J. A.Shared pathways: death receptors and cytotoxic drugs in cancer therapy. Pathol Oncol Res, 2001; 7: 95–106.CrossRefGoogle ScholarPubMed
de Jong, S., Timmer, T., Heijenbrok, F. J., & de Vries, E. G.Death receptor ligands, in particular TRAIL, to overcome drug resistance. Cancer Metastasis Rev, 2001; 20: 51–6.CrossRefGoogle ScholarPubMed
Mitsiades, C. S., Treon, S. P., Mitsiades, N., et al.TRAIL/Apo2L ligand selectively induces apoptosis and overcomes drug resistance in multiple myeloma: therapeutic applications. Blood, 2001; 98: 795–804.CrossRefGoogle ScholarPubMed
Munshi, A., McDonnell, T. J., & Meyn, R. E.Chemotherapeutic agents enhance TRAIL-induced apoptosis in prostate cancer cells. Cancer Chemother Pharmacol, 2002; 50: 46–52.Google ScholarPubMed
Johnston, J. B., Kabore, A. F., Strutinsky, J., et al.Role of the TRAIL/APO2-L death receptors in chlorambucil- and fludarabine-induced apoptosis in chronic lymphocytic leukemia. Oncogene, 2003; 22: 8356–69.CrossRefGoogle ScholarPubMed
Shankar, S. & Srivastava, R. K.Enhancement of therapeutic potential of TRAIL by cancer chemotherapy and irradiation: mechanisms and clinical implications. Drug Resist Updat, 2004; 7: 139–56.CrossRefGoogle ScholarPubMed
Micheau, O., Solary, E., Hammann, A., & Dimanche-Boitrel, M. T.Fas ligand-independent, FADD-mediated activation of the Fas death pathway by anticancer drugs. J Biol Chem, 1999; 274: 7987–92.CrossRefGoogle ScholarPubMed
Hofmann, W. K., de Vos, S., Tsukasaki, K., et al.Altered apoptosis pathways in mantle cell lymphoma detected by oligonucleotide microarray. Blood, 2001; 98: 787–94.CrossRefGoogle ScholarPubMed
Hopkins-Donaldson, S., Ziegler, A., Kurtz, S., et al.Silencing of death receptor and caspase-8 expression in small cell lung carcinoma cell lines and tumors by DNA methylation. Cell Death Differ, 2003; 10: 356–64.CrossRefGoogle ScholarPubMed
Kim, C. H. & Gupta, S.Expression of TRAIL (Apo2L), DR4 (TRAIL receptor 1), DR5 (TRAIL receptor 2) and TRID (TRAIL receptor 3) genes in multidrug resistant human acute myeloid leukemia cell lines that overexpress MDR 1 (HL60/Tax) or MRP (HL60/AR). Int J Oncol, 2000; 16: 1137–9.Google Scholar
Thomas, R. K., Kallenborn, A., Wickenhauser, C., et al.Constitutive expression of c-FLIP in Hodgkin and Reed-Sternberg cells. Am J Pathol, 2002; 160: 1521–8.CrossRefGoogle ScholarPubMed
Dutton, A., O'Neil, J. D., Milner, A. E., et al.Expression of the cellular FLICE-inhibitory protein (c-FLIP) protects Hodgkin's lymphoma cells from autonomous Fas-mediated death. Proc Natl Acad Sci U S A, 2004; 101: 6611–6.CrossRefGoogle ScholarPubMed
Mathas, S., Lietz, A., Anagnostopoulos, I., et al.c-FLIP mediates resistance of Hodgkin/Reed-Sternberg cells to death receptor-induced apoptosis. J Exp Med, 2004; 199: 1041–52.CrossRefGoogle ScholarPubMed
Olsson, A., Diaz, T., Aguilar-Santelises, M., et al.Sensitization to TRAIL-induced apoptosis and modulation of FLICE-inhibitory protein in B chronic lymphocytic leukemia by actinomycin D. Leukemia, 2001; 15: 1868–77.CrossRefGoogle Scholar
MacFarlane, M., Harper, N., Snowden, R. T., et al.Mechanisms of resistance to TRAIL-induced apoptosis in primary B cell chronic lymphocytic leukaemia. Oncogene, 2002; 21: 6809–18.CrossRefGoogle ScholarPubMed
Pedersen, I. M., Kitada, S., Schimmer, A., et al.The triterpenoid CDDO induces apoptosis in refractory CLL B cells. Blood, 2002; 100: 2965–72.CrossRefGoogle ScholarPubMed
Aron, J. L., Parthun, M. R., Marcucci, G., et al.Depsipeptide (FR901228) induces histone acetylation and inhibition of histone deacetylase in chronic lymphocytic leukemia cells concurrent with activation of caspase 8-mediated apoptosis and down-regulation of c-FLIP protein. Blood, 2003; 102: 652–8.CrossRefGoogle ScholarPubMed
Suh, W. S., Kim, Y. S., Schimmer, A. D., et al.Synthetic triterpenoids activate a pathway for apoptosis in AML cells involving downregulation of FLIP and sensitization to TRAIL. Leukemia, 2003; 17: 2122–9.CrossRefGoogle ScholarPubMed
Tang, R., Faussat, A. M., Majdak, P., et al.Valproic acid inhibits proliferation and induces apoptosis in acute myeloid leukemia cells expressing P-gp and MRP1. Leukemia, 2004; 18: 1246–51.CrossRefGoogle ScholarPubMed
Packham, G., White, E. L., Eischen, C. M., et al.Selective regulation of Bcl-XL by a Jak kinase-dependent pathway is bypassed in murine hematopoietic malignancies. Genes Dev, 1998; 12: 2475–87.CrossRefGoogle ScholarPubMed
Adachi, M., Torigoe, T., Takayama, S., & Imai, K.BAG-1 and Bcl-2 in IL-2 signaling. Leuk Lymphoma, 1998; 30: 483–91.CrossRefGoogle ScholarPubMed
Hofmeister, R., Khaled, A. R., Benbernou, N., et al.Interleukin-7: physiological roles and mechanisms of action. Cytokine Growth Factor Rev, 1999; 10: 41–60.CrossRefGoogle ScholarPubMed
Jeffers, J. R., Parganas, E., Lee, Y., et al.Puma is an essential mediator of p53-dependent and -independent apoptotic pathways. Cancer Cell, 2003; 4: 321–8.CrossRefGoogle ScholarPubMed
Shinjyo, T., Kuribara, R., Inukai, T., et al.Downregulation of Bim, a proapoptotic relative of Bcl-2, is a pivotal step in cytokine-initiated survival signaling in murine hematopoietic progenitors. Mol Cell Biol, 2001; 21: 854–64.CrossRefGoogle ScholarPubMed
Villunger, A., Michalak, E. M., Coultas, L., et al.p53- and drug-induced apoptotic responses mediated by BH3-only proteins puma and noxa. Science, 2003; 302: 1036–8.CrossRefGoogle ScholarPubMed
Cantley, L. C. & Neel, B. G.New insights into tumor suppression: PTEN suppresses tumor formation by restraining the phosphoinositide 3-kinase/AKT pathway. Proc Natl Acad Sci U S A, 1999; 96: 4240–5.CrossRefGoogle ScholarPubMed
Chang, F., Lee, J. T., Navolanic, P. M., et al.Involvement of PI3K/Akt pathway in cell cycle progression, apoptosis, and neoplastic transformation: a target for cancer chemotherapy. Leukemia, 2003; 17: 590–603.CrossRefGoogle ScholarPubMed
Paez, J. & Sellers, W. R.PI3K/PTEN/AKT pathway. A critical mediator of oncogenic signaling. Cancer Treat Res, 2003; 115: 145–67.CrossRefGoogle ScholarPubMed
Cantley, L. C.The phosphoinositide 3-kinase pathway. Science, 2002; 296: 1655–7.CrossRefGoogle ScholarPubMed
Fresno Vara, J. A., Casado, E., de Castro, J., et al.PI3K/Akt signalling pathway and cancer. Cancer Treat Rev, 2004; 30: 193–204.CrossRefGoogle ScholarPubMed
Pommier, Y., Sordet, O., Antony, S., Hayward, R. L., & Kohn, K. W.Apoptosis defects and chemotherapy resistance: molecular interaction maps and networks. Oncogene, 2004; 23: 2934–49.CrossRefGoogle ScholarPubMed
Manoukian, A. S. & Woodgett, J. R.Role of glycogen synthase kinase-3 in cancer: regulation by Wnts and other signaling pathways. Adv Cancer Res, 2002; 84: 203–29.CrossRefGoogle ScholarPubMed
Manning, B. D. & Cantley, L. C.Hitting the target: emerging technologies in the search for kinase substrates. Sci STKE, 2002; 162: pe49.Google Scholar
Jaeschke, A., Dennis, P. B., & Thomas, G.mTOR: a mediator of intracellular homeostasis. Curr Top Microbiol Immunol, 2004; 279: 283–98.Google ScholarPubMed
Bjornsti, M. A. & Houghton, P. J.The TOR pathway: a target for cancer therapy. Nat Rev Cancer, 2004; 4: 335–48.CrossRefGoogle ScholarPubMed
Brunet, A., Bonni, A., Zigmond, M. J., et al.Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell, 1999; 96: 857–68.CrossRefGoogle ScholarPubMed
Burgering, B. M. & Medema, R. H.Decisions on life and death: FOXO Forkhead transcription factors are in command when PKB/Akt is off duty. J Leukoc Biol, 2003; 73: 689–701.CrossRefGoogle ScholarPubMed
Cardone, M. H., Roy, N., Stennicke, H. R., et al.Regulation of cell death protease caspase-9 by phosphorylation. Science, 1998; 282: 1318–21.CrossRefGoogle ScholarPubMed
Datta, S. R., Dudek, H., Tao, X., et al.Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell, 1997; 91: 231–41.CrossRefGoogle ScholarPubMed
del Peso, L., Gonzalez-Garcia, M., Page, C., & Herrera, R., & Nunez, G.Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science, 1997; 278: 687–9.CrossRefGoogle ScholarPubMed
Burgering, B. M. & Kops, G. J.Cell cycle and death control: long live Forkheads. Trends Biochem Sci, 2002; 27: 352–60.CrossRefGoogle ScholarPubMed
Zha, J., Harada, H., Yang, E., Jockel, J., & Korsmeyer, S. J.Serine phosphorylation of death agonist BAD in response to survival factor results in binding to 14–3–3 not BCL-X(L). Cell, 1996; 87: 619–28.CrossRefGoogle Scholar
Ali, I. U., Schriml, L. M., & Dean, M.Mutational spectra of PTEN/MMAC1 gene: a tumor suppressor with lipid phosphatase activity. J Natl Cancer Inst, 1999; 91: 1922–32.CrossRefGoogle ScholarPubMed
Sansal, I. & Sellers, W. R.The biology and clinical relevance of the PTEN tumor suppressor pathway. J Clin Oncol, 2004; 22: 2954–63.CrossRefGoogle ScholarPubMed
Nakahara, Y., Nagai, H., Kinoshita, T., et al.Mutational ana lysis of the PTEN/MMAC1 gene in non-Hodgkin's lymphoma. Leukemia, 1998; 12: 1277–80.CrossRefGoogle Scholar
Santos, J., Herranz, M., Fernandez, M., et al.Evidence of a possible epigenetic inactivation mechanism operating on a region of mouse chromosome 19 in gamma-radiation-induced thymic lymphomas. Oncogene, 2001; 20: 2186–9.CrossRefGoogle ScholarPubMed
Butler, M. P., Wang, S. I., Chaganti, R. S., Parsons, R., & Dalla-Favera, R.Analysis of PTEN mutations and deletions in B-cell non-Hodgkin's lymphomas. Genes Chromosomes Cancer, 1999; 24: 322–7.3.0.CO;2-9>CrossRefGoogle ScholarPubMed
Scarisbrick, J. J., Woolford, A. J., Russell-Jones, R., & Whittaker, S. J.Loss of heterozygosity on 10q and microsatellite instability in advanced stages of primary cutaneous T-cell lymphoma and possible association with homozygous deletion of PTEN. Blood, 2000; 95: 2937–42.Google ScholarPubMed
Hyun, T., Yam, A., Pece, S., et al.Loss of PTEN expression leading to high Akt activation in human multiple myelomas. Blood, 2000; 96: 3560–8.Google ScholarPubMed
Roman-Gomez, J., Jimenez-Velasco, A., Castillejo, J. A., et al.Promoter hypermethylation of cancer-related genes is a strong independent prognostic factor in acute lymphoblastic leukemia. Blood, 2004; 104: 2492–8.CrossRefGoogle Scholar
Suzuki, A., de la Pompa, J. L., Stambolic, V., et al.High cancer susceptibility and embryonic lethality associated with mutation of the PTEN tumor suppressor gene in mice. Curr Biol, 1998; 8: 1169–78.CrossRefGoogle ScholarPubMed
Wu, H., Goel, V., & Haluska, F. G.PTEN signaling pathways in melanoma. Oncogene, 2003; 22: 3113–22.CrossRefGoogle ScholarPubMed
Bianco, R., Shin, I., Ritter, C. A., et al.Loss of PTEN/MMAC1/TEP in EGF receptor-expressing tumor cells counteracts the antitumor action of EGFR tyrosine kinase inhibitors. Oncogene, 2003; 22: 2812–22.CrossRefGoogle ScholarPubMed
Soengas, M. S. & Lowe, S. W.Apoptosis and melanoma chemoresistance. Oncogene, 2003; 22: 3138–51.CrossRefGoogle ScholarPubMed
Zhou, M., Gu, L., Findley, H. W., Jiang, R., & Woods, W. G.PTEN reverses MDM2-mediated chemotherapy resistance by interacting with p53 in acute lymphoblastic leukemia cells. Cancer Res, 2003; 63: 6357–62.Google ScholarPubMed
Tang, D., Okada, H., Ruland, J., et al.Akt is activated in response to an apoptotic signal. J Biol Chem, 2001; 276: 30 461–6.CrossRefGoogle Scholar
Karpinich, N. O., Tafani, M., Rothman, R. J., Russo, M. A., & Farber, J. L.The course of etoposide-induced apoptosis from damage to DNA and p53 activation to mitochondrial release of cytochrome c. J Biol Chem, 2002; 277: 16 547–52.CrossRefGoogle ScholarPubMed
Staal, S. P.Molecular cloning of the akt oncogene and its human homologues AKT1 and AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma. Proc Natl Acad Sci U S A, 1987; 84: 5034–7.CrossRefGoogle Scholar
Cheng, J. Q., Godwin, A. K., Bellacosa, A., et al.AKT2, a putative oncogene encoding a member of a subfamily of protein-serine/threonine kinases, is amplified in human ovarian carcinomas. Proc Natl Acad Sci U S A, 1992; 89: 9267–71.CrossRefGoogle ScholarPubMed
Bellacosa, A., de Feo, D., Godwin, A. K., et al.Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas. Int J Cancer, 1995; 64: 280–5.CrossRefGoogle ScholarPubMed
Cheng, J. Q., Ruggeri, B., Klein, W. M., et al.Amplification of AKT2 in human pancreatic cells and inhibition of AKT2 expression and tumorigenicity by antisense RNA. Proc Natl Acad Sci U S A, 1996; 93: 3636–41.CrossRefGoogle ScholarPubMed
Ruggeri, B. A., Huang, L., Wood, M., Cheng, J. Q., & Testa, J. R.Amplification and overexpression of the AKT2 oncogene in a subset of human pancreatic ductal adenocarcinomas. Mol Carcinog, 1998; 21: 81–6.3.0.CO;2-R>CrossRefGoogle Scholar
Arranz, E., Robledo, M., Martinez, B., et al.Incidence of homogeneously staining regions in non-Hodgkin lymphomas. Cancer Genet Cytogenet, 1996; 87: 1–3.CrossRefGoogle ScholarPubMed
Mitsiades, C. S., Mitsiades, N., & Koutsilieris, M.The Akt pathway: molecular targets for anti-cancer drug development. Curr Cancer Drug Targets, 2004; 4: 235–56.CrossRefGoogle ScholarPubMed
Tabellini, G., Cappellini, A., Tazzari, P. L., et al.Phosphoinositide 3-kinase/Akt involvement in arsenic trioxide resistance of human leukemia cells. J Cell Physiol, 2005; 202: 623–34.CrossRefGoogle ScholarPubMed
Dai, Y., Rahmani, M., Pei, X. Y., Dent, P., & Grant, S.Bortezomib and flavopiridol interact synergistically to induce apoptosis in chronic myeloid leukemia cells resistant to imatinib mesylate through both Bcr/Abl-dependent and -independent mechanisms. Blood, 2004; 104: 509–18.CrossRefGoogle ScholarPubMed
Shayesteh, L., Lu, Y., Kuo, W. L., et al.PIK3CA is implicated as an oncogene in ovarian cancer. Nat Genet, 1999; 21: 99–102.CrossRefGoogle ScholarPubMed
Woenckhaus, J., Steger, K., Werner, E., et al.Genomic gain of PIK3CA and increased expression of p110alpha are associated with progression of dysplasia into invasive squamous cell carcinoma. J Pathol, 2002; 198: 335–42.CrossRefGoogle ScholarPubMed
Byun, D. S., Cho, K., Ryu, B. K., et al.Frequent monoallelic deletion of PTEN and its reciprocal association with PIK3CA amplification in gastric carcinoma. Int J Cancer, 2003; 104: 318–27.CrossRefGoogle Scholar
Mao, X., Orchard, G., Lillington, D. M., et al.Amplification and overexpression of JUNB is associated with primary cutaneous T-cell lymphomas. Blood, 2003; 101: 1513–19.CrossRefGoogle ScholarPubMed
Wendel, H. G., De Stanchina, E., Fridman, J. S., et al.Survival signalling by Akt and eIF4E in oncogenesis and cancer therapy. Nature, 2004; 428: 332–7.CrossRefGoogle ScholarPubMed
Li, Q. & Zhu, G. D.Targeting serine/threonine protein kinase B/Akt and cell-cycle checkpoint kinases for treating cancer. Curr Top Med Chem, 2002; 2: 939–71.CrossRefGoogle ScholarPubMed
Xia, W., Mullin, R. J., Keith, B. R., et al.Anti-tumor activity of GW572016: a dual tyrosine kinase inhibitor blocks EGF activation of EGFR/erbB2 and downstream Erk1/2 and AKT pathways. Oncogene, 2002; 21: 6255–63.CrossRefGoogle ScholarPubMed
Yang, L., Dan, H. C., Sun, M., et al.Akt/protein kinase B signaling inhibitor-2, a selective small molecule inhibitor of Akt signaling with antitumor activity in cancer cells overexpressing Akt. Cancer Res, 2004; 64: 4394–9.CrossRefGoogle ScholarPubMed
Sen, R. & Baltimore, D.Inducibility of kappa immunoglobulin enhancer-binding protein NF-kappa B by a posttranslational mechanism. Cell, 1986; 47: 921–8.CrossRefGoogle ScholarPubMed
Baldwin, A. S.Control of oncogenesis and cancer therapy resistance by the transcription factor NF-kappa B. J Clin Invest, 2001; 107: 241–6.CrossRefGoogle Scholar
Chen, C., Edelstein, L. C. & Gelinas, C.The Rel/NF-kappa B family directly activates expression of the apoptosis inhibitor Bcl-x(L). Mol Cell Biol, 2000; 20: 2687–95.CrossRefGoogle Scholar
Shishodia, S. & Aggarwal, B. B.Guggulsterone inhibits NF-kB and IkBa kinase activation, suppresses expression of antiapoptotic gene products and enhances apoptosis. J Biol Chem, 2004; 279: 47 148–58.CrossRefGoogle Scholar
Chen, L., Fischle, W., Verdin, E., & Greene, W. C.Duration of nuclear NF-kappa B action regulated by reversible acetylation. Science, 2001; 293: 1653–7.CrossRefGoogle Scholar
Chen, L. F., Mu, Y., & Greene, W. C.Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kappa B. EMBO J, 2002; 21: 6539–48.CrossRefGoogle Scholar
Karin, M. & Delhase, M.The I kappa B kinase (IKK) and NF-kappa B: key elements of proinflammatory signalling. Semin Immunol, 2000; 12: 85–98.CrossRefGoogle ScholarPubMed
Yamamoto, Y. & Gaynor, R. B.Ikappa B kinases: key regulators of the NF-kappa B pathway. Trends Biochem Sci, 2004; 29: 72–9.CrossRefGoogle Scholar
Baud, V. & Karin, M.Signal transduction by tumor necrosis factor and its relatives. Trends Cell Biol, 2001; 11: 372–7.CrossRefGoogle ScholarPubMed
Singh, H.Genetic analysis of transcription factors implicated in B lymphocyte development. Immunol Res, 1994; 13: 280–90.CrossRefGoogle ScholarPubMed
Beg, A. A., Sha, W. C., Bronson, R. T., & Baltimore, D.Constitutive NF-kappa B activation, enhanced granulopoiesis, and neonatal lethality in Ikappa B alpha-deficient mice. Genes Dev, 1995; 9: 2736–46.CrossRefGoogle Scholar
Klement, J. F., Rice, N. R., Car, B. D., et al.IkappaBalpha deficiency results in a sustained NF-kappaB response and severe widespread dermatitis in mice. Mol Cell Biol, 1996; 16: 2341–9.CrossRefGoogle Scholar
Ishikawa, H., Carrasco, D., Claudio, E., Ryseck, R. P., & Bravo, R.Gastric hyperplasia and increased proliferative responses of lymphocytes in mice lacking the COOH-terminal ankyrin domain of NF-kappaB2. J Exp Med, 1997; 186: 999–1014.CrossRefGoogle ScholarPubMed
Ishikawa, H., Claudio, E., Dambach, D., et al.Chronic inflammation and susceptibility to bacterial infections in mice lacking the polypeptide (p)105 precursor (NF-kappaB1) but expressing p50. J Exp Med, 1998; 187: 985–96.CrossRefGoogle ScholarPubMed
Schwarz, E. M., Krimpenfort, P., Berns, A., & Verma, I. M.Immunological defects in mice with a targeted disruption in Bcl-3. Genes Dev, 1997; 11: 187–97.CrossRefGoogle ScholarPubMed
Ouaaz, F., Li, M., & Beg, A. A.A critical role for the RelA subunit of nuclear factor kappa B in regulation of multiple immune-response genes and in Fas-induced cell death. J Exp Med, 1999; 189: 999–1004.CrossRefGoogle ScholarPubMed
Takeda, K., Takeuchi, O., Tsujimura, T., et al.Limb and skin abnormalities in mice lacking IKKalpha. Science, 1999; 284: 313–16.CrossRefGoogle ScholarPubMed
Rudolph, D., Yeh, W. C., Wakeham, A., et al.Severe liver degeneration and lack of NF-kappa B activation in NEMO/IKKgamma-deficient mice. Genes Dev, 2000; 14: 854–62.Google ScholarPubMed
Wang, C. Y., Mayo, M. W., Korneluk, R. G., Goeddel, D. V., & Baldwin, A. S. Jr.NF-kappa B antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science, 1998; 281: 1680–3.CrossRefGoogle ScholarPubMed
Deveraux, Q. L., Roy, N., Stennicke, H. R., et al.IAPs block apoptotic events induced by caspase-8 and cytochrome c by direct inhibition of distinct caspases. EMBO J, 1998; 17: 2215–23.CrossRefGoogle ScholarPubMed
Notarbartolo, M., Cervello, M., Poma, P., et al.Expression of the IAPs in multidrug resistant tumor cells. Oncol Rep, 2004; 11: 133–6.Google ScholarPubMed
Kasibhatla, S., Genestier, L., & Green, D. R.Regulation of fas-ligand expression during activation-induced cell death in T lymphocytes via nuclear factor kappa B. J Biol Chem, 1999; 274: 987–92.CrossRefGoogle Scholar
Li, N. & Karin, M.Ionizing radiation and short wavelength UV activate NF-kappaB through two distinct mechanisms. Proc Natl Acad Sci U S A, 1998; 95: 13 012–17.CrossRefGoogle ScholarPubMed
Yan, C., Wang, H., & Boyd, D. D.KiSS-1 represses 92-kDa type IV collagenase expression by down-regulating NF-kappa B binding to the promoter as a consequence of Ikappa Balpha-induced block of p65/p50 nuclear translocation. J Biol Chem, 2001; 276: 1164–72.CrossRefGoogle ScholarPubMed
Wu, M., Lee, H., Bellas, R. E., et al.Inhibition of NF-kappaB/Rel induces apoptosis of murine B cells. EMBO J, 1996; 15: 4682–90.Google ScholarPubMed
Antwerp, D. J., Martin, S. J., Kafri, T., Green, D. R., & Verma, I. M.Suppression of TNF-alpha-induced apoptosis by NF-kappaB. Science, 1996; 274: 787–9.CrossRefGoogle ScholarPubMed
Ehrhardt, H., Fulda, S., Schmid, I., et al.TRAIL induced survival and proliferation in cancer cells resistant towards TRAIL-induced apoptosis mediated by NF-kappaB. Oncogene, 2003; 22: 3842–52.CrossRefGoogle ScholarPubMed
Prasad, A. V., Mohan, N., Chandrasekar, B., & Meltz, M. L.Activation of nuclear factor kappa B in human lymphoblastoid cells by low-dose ionizing radiation. Radiat Res, 1994; 138: 367–72.CrossRefGoogle ScholarPubMed
Pahl, H. L.Activators and target genes of Rel/NF-kappaB transcription factors. Oncogene, 1999; 18: 6853–66.CrossRefGoogle ScholarPubMed
Viatour, P., Bentires-Alj, M., Chariot, A., et al.NF-kappa B2/p100 induces Bcl-2 expression. Leukemia, 2003; 17: 1349–56.CrossRefGoogle ScholarPubMed
Mori, N., Fujii, M., Ikeda, S., et al.Constitutive activation of NF-kappaB in primary adult T-cell leukemia cells. Blood, 1999; 93: 2360–8.Google ScholarPubMed
Garg, A. & Aggarwal, B. B.Nuclear transcription factor-kappaB as a target for cancer drug development. Leukemia, 2002; 16: 1053–68.CrossRefGoogle ScholarPubMed
Paillard, F.Induction of apoptosis with I-kappaB, the inhibitor of NF-kappaB. Hum Gene Ther, 1999; 10: 1–3.CrossRefGoogle ScholarPubMed
Gilmore, T. D., Starczynowski, D. T., & Kalaitzidis, D.RELevant gene amplification in B-cell lymphomas ?Blood, 2004; 103: 3243–4, author reply 4–5.CrossRefGoogle ScholarPubMed
Migliazza, A., Lombardi, L., Rocchi, M., et al.Heterogen eous chromosomal aberrations generate 3′ truncations of the NFKB2/lyt-10 gene in lymphoid malignancies. Blood, 1994; 84: 3850–60.Google Scholar
Thakur, S., Lin, H. C., Tseng, W. T., et al.Rearrangement and altered expression of the NFKB-2 gene in human cutaneous T-lymphoma cells. Oncogene, 1994; 9: 2335–44.Google ScholarPubMed
Zhang, Q., Siebert, R., Yan, M., et al.Inactivating mutations and overexpression of BCL10, a caspase recruitment domain-containing gene, in MALT lymphoma with t(1;14)(p22;q32). Nat Genet, 1999; 22: 63–8.CrossRefGoogle Scholar
Cuni, S., Perez-Aciego, P., Perez-Chacon, G., et al.A sustained activation of PI3K/NF-kappaB pathway is critical for the survival of chronic lymphocytic leukemia B cells. Leukemia, 2004; 18: 1391–400.CrossRefGoogle ScholarPubMed
Bueso-Ramos, C. E., Rocha, F. C., Shishodia, S., et al.Expression of constitutively active nuclear-kappa B RelA transcription factor in blasts of acute myeloid leukemia. Hum Pathol, 2004; 35: 246–53.CrossRefGoogle ScholarPubMed
Birkenkamp, K. U., Geugien, M., Schepers, H., et al.Constitutive NF-kappaB DNA-binding activity in AML is frequently mediated by a Ras/PI3-K/PKB-dependent pathway. Leukemia, 2004; 18: 103–12.CrossRefGoogle Scholar
Baumgartner, B., Weber, M., Quirling, M., et al.Increased IkappaB kinase activity is associated with activated NF-kappaB in acute myeloid blasts. Leukemia, 2002; 16: 2062–71.CrossRefGoogle ScholarPubMed
Kordes, U., Krappmann, D., Heissmeyer, V., Ludwig, W. D., & Scheidereit, C.Transcription factor NF-kappaB is constitutively activated in acute lymphoblastic leukemia cells. Leukemia, 2000; 14: 399–402.CrossRefGoogle ScholarPubMed
Bharti, A. C., Shishodia, S., Reuben, J. M., et al.Nuclear factor-kappaB and STAT3 are constitutively active in CD138+ cells derived from multiple myeloma patients, and suppression of these transcription factors leads to apoptosis. Blood, 2004; 103: 3175–84.CrossRefGoogle Scholar
Horie, R. & Watanabe, T.The biological basis of Hodgkin's lymphoma. Drug News Perspect, 2003; 16: 649–56.CrossRefGoogle ScholarPubMed
Savage, K. J., Monti, S., Kutok, J. L., et al.The molecular signature of mediastinal large B-cell lymphoma differs from that of other diffuse large B-cell lymphomas and shares features with classical Hodgkin lymphoma. Blood, 2003; 102: 3871–9.CrossRefGoogle ScholarPubMed
Pham, L. V., Tamayo, A. T., Yoshimura, L. C., Lo, P., & Ford, R. J.Inhibition of constitutive NF-kappa B activation in mantle cell lymphoma B cells leads to induction of cell cycle arrest and apoptosis. J Immunol, 2003; 171: 88–95.CrossRefGoogle ScholarPubMed
Griffin, J. D.Leukemia stem cells and constitutive activation of NF-kappaB. Blood, 2001; 98: 2291.CrossRefGoogle ScholarPubMed
Weston, V. J., Austen, B., Wei, W., et al.Apoptotic resistance to ionizing radiation in pediatric B-precursor acute lymphoblastic leukemia frequently involves increased NF-kappaB survival pathway signaling. Blood, 2004; 104: 1465–73.CrossRefGoogle ScholarPubMed
Hideshima, T., Chauhan, D., Richardson, P., et al.NF-kappa B as a therapeutic target in multiple myeloma. J Biol Chem, 2002; 277: 16 639–47.CrossRefGoogle ScholarPubMed
Giri, D. K. & Aggarwal, B. B.Constitutive activation of NF-kappaB causes resistance to apoptosis in human cutaneous T cell lymphoma HuT-78 cells. Autocrine role of tumor necrosis factor and reactive oxygen intermediates. J Biol Chem, 1998; 273: 14 008–14.CrossRefGoogle ScholarPubMed
Reuther, J. Y., Reuther, G. W., Cortez, D., Pendergast, A. M., & Baldwin, A. S. Jr.A requirement for NF-kappaB activation in Bcr-Abl-mediated transformation. Genes Dev, 1998; 12: 968–81.CrossRefGoogle ScholarPubMed
Flynn, V. Jr., Ramanitharan, A., Moparty, K., et al.Adenovirus-mediated inhibition of NF-kappaB confers chemo-sensitization and apoptosis in prostate cancer cells. Int J Oncol, 2003; 23: 317–23.Google ScholarPubMed
Cusack, J. C.Rationale for the treatment of solid tumors with the proteasome inhibitor bortezomib. Cancer Treat Rev, 2003; 29 (Suppl. 1): 21–31.CrossRefGoogle ScholarPubMed
Frantz, B. & O'Neill, E. A.The effect of sodium salicylate and aspirin on NF-kappa B. Science, 1995; 270: 2017–19.CrossRefGoogle ScholarPubMed
Kapahi, P., Takahashi, T., Natoli, G., et al.Inhibition of NF-kappa B activation by arsenite through reaction with a critical cysteine in the activation loop of Ikappa B kinase. J Biol Chem, 2000; 275: 36 062–6.CrossRefGoogle ScholarPubMed
D'Acquisto, F., Ialenti, A., Ianaro, A., Di Vaio, R., & Carnuccio, R.Local administration of transcription factor decoy oligonucleotides to nuclear factor-kappaB prevents carrageenin-induced inflammation in rat hind paw. Gene Ther, 2000; 7: 1731–7.CrossRefGoogle ScholarPubMed
Orlowski, R. Z. & Baldwin, A. S. Jr.NF-kappaB as a therapeutic target in cancer. Trends Mol Med, 2002; 8: 385–9.CrossRefGoogle Scholar
Epinat, J. C. & Gilmore, T. D.Diverse agents act at multiple levels to inhibit the Rel/NF-kappaB signal transduction pathway. Oncogene, 1999; 18: 6896–909.CrossRefGoogle ScholarPubMed
El-Deiry, W. S.p21/p53, cellular growth control and genomic integrity. Curr Top Microbiol Immunol, 1998; 227: 121–37.Google ScholarPubMed
Hollstein, M., Hergenhahn, M., Yang, Q., et al.New approaches to understanding p53 gene tumor mutation spectra. Mutat Res, 1999; 431: 199–209.CrossRefGoogle ScholarPubMed
El-Deiry, W. S.The role of p53 in chemosensitivity and radiosensitivity. Oncogene, 2003; 22: 7486–95.CrossRefGoogle ScholarPubMed
Fridman, J. S. & Lowe, S. W.Control of apoptosis by p53. Oncogene, 2003; 22: 9030–40.CrossRefGoogle ScholarPubMed
Gasco, M. & Crook, T.p53 family members and chemoresistance in cancer: what we know and what we need to know. Drug Resist Updat, 2003; 6: 323–8.CrossRefGoogle ScholarPubMed
Olivier, M., Hussain, S. P., Caron de Fromentel, C., Hainaut, P., & Harris, C. C.TP53 mutation spectra and load: a tool for generating hypotheses on the etiology of cancer. IARC Sci Publ, 2004; 157: 247–70.Google Scholar
Peller, S. & Rotter, V.TP53 in hematological cancer: low incidence of mutations with significant clinical relevance. Hum Mutat, 2003; 21: 277–84.CrossRefGoogle ScholarPubMed
Hirokawa, M., Kawabata, Y., & Miura, A. B.Dysregulation of apoptosis and a novel mechanism of defective apoptotic signal transduction in human B-cell neoplasms. Leuk Lymphoma, 2002; 43: 243–9.CrossRefGoogle Scholar
Di Bacco, A., Keeshan, K., McKenna, S. L., & Cotter, T. G.Molecular abnormalities in chronic myeloid leukemia: deregulation of cell growth and apoptosis. Oncologist, 2000; 5: 405–15.CrossRefGoogle ScholarPubMed
Stilgenbauer, S., Lichter, P., & Dohner, H.Genetic features of B-cell chronic lymphocytic leukemia. Rev Clin Exp Hematol, 2000; 4: 48–72.CrossRefGoogle ScholarPubMed
Newcomb, E. W., el Rouby, S., & Thomas, A.A unique spectrum of p53 mutations in B-cell chronic lymphocytic leukemia distinct from that of other lymphoid malignancies. Mol Carcinog, 1995; 14: 227–32.CrossRefGoogle ScholarPubMed
Momand, J., Zambetti, G. P., Olson, D. C., George, D., & Levine, A. J.The mdm-2 oncogene product forms a complex with the p53 protein and inhibits p53-mediated transactivation. Cell, 1992; 69: 1237–45.CrossRefGoogle ScholarPubMed
Fuchs, S. Y., Adler, V., Buschmann, T., Wu, X., & Ronai, Z.Mdm2 association with p53 targets its ubiquitination. Oncogene, 1998; 17: 2543–7.CrossRefGoogle ScholarPubMed
Banin, S., Moyal, L., Shieh, S., et al.Enhanced phosphorylation of p53 by ATM in response to DNA damage. Science, 1998; 281: 1674–7.CrossRefGoogle ScholarPubMed
Canman, C. E., Lim, D. S., Cimprich, K. A., et al.Activation of the ATM kinase by ionizing radiation and phosphorylation of p53. Science, 1998; 281: 1677–9.CrossRefGoogle ScholarPubMed
Pomerantz, J., Schreiber-Agus, N., Liegeois, N. J., et al.The Ink4a tumor suppressor gene product, p19Arf, interacts with MDM2 and neutralizes MDM2's inhibition of p53. Cell, 1998; 92: 713–23.CrossRefGoogle ScholarPubMed
Weber, J. D., Taylor, L. J., Roussel, M. F., Sherr, C. J., & Bar-Sagi, D.Nucleolar Arf sequesters Mdm2 and activates p53. Nat Cell Biol, 1999; 1: 20–6.CrossRefGoogle ScholarPubMed
Vousden, K. H. & Lu, X.Live or let die: the cell's response to p53. Nat Rev Cancer, 2002; 2: 594–604.CrossRefGoogle ScholarPubMed
Donehower, L. A., Harvey, M., Slagle, B. L., et al.Mice deficient for p53 are developmentally normal but susceptible to spontaneous tumours. Nature, 1992; 356: 215–21.CrossRefGoogle ScholarPubMed
Lowe, S. W., Jacks, T., Housman, D. E., & Ruley, H. E.Abrogation of oncogene-associated apoptosis allows transformation of p53-deficient cells. Proc Natl Acad Sci U S A, 1994; 91: 2026–30.CrossRefGoogle ScholarPubMed
Schmitt, C. A., Fridman, J. S., Yang, M., et al.A senescence program controlled by p53 and p16INK4a contributes to the outcome of cancer therapy. Cell, 2002; 109: 335–46.CrossRefGoogle ScholarPubMed
Hainaut, P. & Hollstein, M.p53 and human cancer: the first ten thousand mutations. Adv Cancer Res, 2000; 77: 81–137.CrossRefGoogle ScholarPubMed
Zheng, A., Castren, K., Saily, M., et al.p53 status of newly established acute myeloid leukaemia cell lines. Br J Cancer, 1999; 79: 407–15.CrossRefGoogle ScholarPubMed
Isaacson, P. G.Gastric MALT lymphoma: from concept to cure. Ann Oncol, 1999; 10: 637–45.CrossRefGoogle Scholar
Whittaker, S.Clinical and prognostic significance of molecular studies in cutaneous T-cell lymphoma. Curr Top Pathol, 2001; 94: 93–101.CrossRefGoogle ScholarPubMed
Lindstrom, M. S. & Wiman, K. G.Role of genetic and epigenetic changes in Burkitt lymphoma. Semin Cancer Biol, 2002; 12: 381–7.CrossRefGoogle ScholarPubMed
Momand, J. & Zambetti, G. P.Mdm-2: “big brother” of p53. J Cell Biochem, 1997; 64: 343–52.3.0.CO;2-V>CrossRefGoogle ScholarPubMed
Momand, J., Jung, D., Wilczynski, S., & Niland, J.The MDM2 gene amplification database. Nucleic Acids Res, 1998; 26: 3453–9.CrossRefGoogle ScholarPubMed
Ridge, S. A., Dyer, M., Greaves, M. F., & Wiedemann, L. M.Lack of MDM2 amplification in human leukaemia. Br J Haematol, 1994; 86: 407–9.CrossRefGoogle ScholarPubMed
Cesarman, E., Liu, Y. F., & Knowles, D. M.The MDM2 oncogene is rarely amplified in human lymphoid tumors and does not correlate with p53 gene expression. Int J Cancer, 1994; 56: 457–8.CrossRefGoogle Scholar
Huang, Y. Q., Raphael, B., Buchbinder, A., et al.Rearrangement and expression of MDM2 oncogene in chronic lymphocytic leukemia. Am J Hematol, 1994; 47: 139–41.CrossRefGoogle ScholarPubMed
Merup, M., Juliusson, G., Wu, X., et al.Amplification of multiple regions of chromosome 12, including 12q13–15, in chronic lymphocytic leukaemia. Eur J Haematol, 1997; 58: 174–80.CrossRefGoogle ScholarPubMed
Kupper, M., Joos, S., Bonin, F. von, et al.MDM2 gene amplification and lack of p53 point mutations in Hodgkin and Reed-Sternberg cells: results from single-cell polymerase chain reaction and molecular cytogenetic studies. Br J Haematol, 2001; 112: 768–75.CrossRefGoogle ScholarPubMed
Elnenaei, M. O., Gruszka-Westwood, A. M., A'Hernt, R., et al.Gene abnormalities in multiple myeloma; the relevance of TP53, MDM2, and CDKN2A. Haematologica, 2003; 88: 529–37.Google ScholarPubMed
Rao, P. H., Houldsworth, J., Dyomina, K., et al.Chromosomal and gene amplification in diffuse large B-cell lymphoma. Blood, 1998; 92: 234–40.Google ScholarPubMed
Bueso-Ramos, C. E., Yang, Y., deLeon, E., et al.The human MDM-2 oncogene is overexpressed in leukemias. Blood, 1993; 82: 2617–23.Google ScholarPubMed
Quesnel, B., Preudhomme, C., Fournier, J., Fenaux, P., & Peyrat, J. P.MDM2 gene amplification in human breast cancer. Eur J Cancer, 1994; 30A: 982–4.CrossRefGoogle ScholarPubMed
Watanabe, T., Hotta, T., Ichikawa, A., et al.The MDM2 oncogene overexpression in chronic lymphocytic leukemia and low-grade lymphoma of B-cell origin. Blood, 1994; 84: 3158–65.Google ScholarPubMed
Watanabe, T., Ichikawa, A., Saito, H., & Hotta, T.Overexpression of the MDM2 oncogene in leukemia and lymphoma. Leuk Lymphoma, 1996; 21: 391–7.CrossRefGoogle ScholarPubMed
Zhou, M., Yeager, A. M., Smith, S. D., & Findley, H. W.Overexpression of the MDM2 gene by childhood acute lymphoblastic leukemia cells expressing the wild-type p53 gene. Blood, 1995; 85: 1608–14.Google ScholarPubMed
Kawamata, N., Miller, C., Levy, V., et al.mdm-2 oncogene expression in non-Hodgkin's lymphomas. Diagn Mol Pathol, 1996; 5: 33–8.CrossRefGoogle ScholarPubMed
Capoulade, C., Bressac-de Paillerets, B., Lefrere, I., et al.Overexpression of MDM2, due to enhanced translation, results in inactivation of wild-type p53 in Burkitt's lymphoma cells. Oncogene, 1998; 16: 1603–10.CrossRefGoogle ScholarPubMed
Gustafsson, B., Christenson, B., Hjalmar, V., & Winiarski, J.Cellular expression of MDM2 and p53 in childhood leukemias with poor prognosis. Med Pediatr Oncol, 2000; 34: 117–24.3.0.CO;2-8>CrossRefGoogle ScholarPubMed
Quelle, D. E., Zindy, F., Ashmun, R. A., & Sherr, C. J.Alternative reading frames of the INK4a tumor suppressor gene encode two unrelated proteins capable of inducing cell cycle arrest. Cell, 1995; 83: 993–1000.Google ScholarPubMed
Honda, R. & Yasuda, H.Association of p19(ARF) with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53. EMBO J, 1999; 18: 22–7.CrossRefGoogle ScholarPubMed
Sherr, C. J. & Weber, J. D.The ARF/p53 pathway. Curr Opin Genet Dev, 2000; 10: 94–9.CrossRefGoogle ScholarPubMed
Kamijo, T., Zindy, F., Roussel, M. F., et al.Tumor suppression at the mouse INK4a locus mediated by the alternative reading frame product p19ARF. Cell, 1997; 91: 649–59.CrossRefGoogle ScholarPubMed
Eischen, C. M., Weber, J. D., Roussel, M. F., Sherr, C. J., & Cleveland, J. L.Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis. Genes Dev, 1999; 13: 2658–69.CrossRefGoogle ScholarPubMed
James, M. C. & Peters, G.Alternative product of the p16/CKDN2A locus connects the Rb and p53 tumor suppressors. Prog Cell Cycle Res, 2000; 4: 71–81.CrossRefGoogle ScholarPubMed
Zindy, F., Eischen, C. M., Randle, D. H., et al.Myc signaling via the ARF tumor suppressor regulates p53-dependent apoptosis and immortalization. Genes Dev, 1998; 12: 2424–33.CrossRefGoogle ScholarPubMed
Weber, J. D., Jeffers, J. R., Rehg, J. E., et al.p53-independent functions of the p19(ARF) tumor suppressor. Genes Dev, 2000; 14: 2358–65.CrossRefGoogle ScholarPubMed
Sugimoto, M., Kuo, M. L., Roussel, M. F., & Sherr, C. J.Nucleolar Arf tumor suppressor inhibits ribosomal RNA processing. Mol Cell, 2003; 11: 415–24.CrossRefGoogle ScholarPubMed
Qi, Y., Gregory, M. A., Li, Z., et al.p19(ARF) directly and differentially controls the functions of c-Myc independently of p53. Nature, 2004; 431: 712–17.CrossRefGoogle Scholar
Cayuela, J. M., Gardie, B., & Sigaux, F.Disruption of the multiple tumor suppressor gene MTS1/p16(INK4a)/CDKN2 by illegitimate V(D)J recombinase activity in T-cell acute lymphoblastic leukemias. Blood, 1997; 90: 3720–6.Google Scholar
Cayuela, J. M., Hebert, J., & Sigaux, F.Homozygous MTS1 (p16INK4A) deletion in primary tumor cells of 163 leukemic patients. Blood, 1995; 85: 854.Google ScholarPubMed
Cayuela, J. M., Madani, A., Sanhes, L., Stern, M. H., & Sigaux, F.Multiple tumor-suppressor gene 1 inactivation is the most frequent genetic alteration in T-cell acute lymphoblastic leukemia. Blood, 1996; 87: 2180–6.Google ScholarPubMed
Faderl, S., Kantarjian, H. M., Estey, E., et al.The prognostic significance of p16(INK4a)/p14(ARF) locus deletion and MDM-2 protein expression in adult acute myelogenous leukemia. Cancer, 2000; 89: 1976–82.3.3.CO;2-E>CrossRefGoogle ScholarPubMed
Hernandez-Boluda, J. C., Cervantes, F., Colomer, D., et al.Genomic p16 abnormalities in the progression of chronic myeloid leukemia into blast crisis: a sequential study in 42 patients. Exp Hematol, 2003; 31: 204–10.CrossRefGoogle ScholarPubMed
Pinyol, M., Hernandez, L., Martinez, A., et al.INK4a/ARF locus alterations in human non-Hodgkin's lymphomas mainly occur in tumors with wild-type p53 gene. Am J Pathol, 2000; 156: 1987–96.CrossRefGoogle ScholarPubMed
Nakamura, M., Sakaki, T., Hashimoto, H., et al.Frequent alterations of the p14(ARF) and p16(INK4a) genes in primary central nervous system lymphomas. Cancer Res, 2001; 61: 6335–9.Google ScholarPubMed
Hayashi, Y., Iwato, M., Arakawa, Y., et al.Homozygous deletion of INK4a/ARF genes and overexpression of bcl-2 in relation with poor prognosis in immunocompetent patients with primary central nervous system lymphoma of the diffuse large B-cell type. J Neurooncol, 2001; 55: 51–8.CrossRefGoogle ScholarPubMed
Maloney, K. W., McGavran, L., Odom, L. F., & Hunger, S. P.Acquisition of p16(INK4A) and p15(INK4B) gene abnormalities between initial diagnosis and relapse in children with acute lymphoblastic leukemia. Blood, 1999; 93: 2380–5.Google ScholarPubMed
Carter, T. L., Reaman, G. H., & Kees, U. R.INK4A/ARF deletions are acquired at relapse in childhood acute lymphoblastic leukaemia: a paired study on 25 patients using real-time polymerase chain reaction. Br J Haematol, 2001; 113: 323–8.CrossRefGoogle ScholarPubMed
Carter, T. L., Watt, P. M., Kumar, R., et al.Hemizygous p16(INK4A) deletion in pediatric acute lymphoblastic leukemia predicts independent risk of relapse. Blood, 2001; 97: 572–4.CrossRefGoogle ScholarPubMed
Duro, D., Bernard, O., Della Valle, V., et al.Inactivation of the P16INK4/MTS1 gene by a chromosome translocation t(9;14)(p21–22;q11) in an acute lymphoblastic leukemia of B-cell type. Cancer Res, 1996; 56: 848–54.Google Scholar
Baur, A. S., Shaw, P., Burri, N., et al.Frequent methylation silencing of p15(INK4b) (MTS2) and p16(INK4a) (MTS1) in B-cell and T-cell lymphomas. Blood, 1999; 94: 1773–81.Google ScholarPubMed
Taniguchi, T., Chikatsu, N., Takahashi, S., et al.Expression of p16INK4A and p14ARF in hematological malignancies. Leukemia, 1999; 13: 1760–9.CrossRefGoogle ScholarPubMed
Christiansen, D. H., Andersen, M. K., & Pedersen-Bjergaard, J.Methylation of p15INK4B is common, is associated with deletion of genes on chromosome arm 7q and predicts a poor prognosis in therapy-related myelodysplasia and acute myeloid leukemia. Leukemia, 2003; 17: 1813–19.CrossRefGoogle ScholarPubMed
Gonzalez-Gomez, P., Bello, M. J., Arjona, D., et al.CpG island methylation of tumor-related genes in three primary central nervous system lymphomas in immunocompetent patients. Cancer Genet Cytogenet, 2003; 142: 21–4.CrossRefGoogle ScholarPubMed
Kastan, M. B., Lim, D. S., Kim, S. T., Xu, B., & Canman, C.Mul tiple signaling pathways involving ATM. Cold Spring Harb Symp Quant Biol, 2000; 65: 521–6.CrossRefGoogle Scholar
Melino, G., Lu, X., Gasco, M., Crook, T., & Knight, R. A.Functional regulation of p73 and p63: development and cancer. Trends Biochem Sci, 2003; 28: 663–70.CrossRefGoogle ScholarPubMed
Westfall, M. D. & Pietenpol, J. A.p63: molecular complexity in development and cancer. Carcinogenesis, 2004; 25: 857–64.CrossRefGoogle ScholarPubMed
Gumy-Pause, F., Wacker, P., & Sappino, A. P.ATM gene and lymphoid malignancies. Leukemia, 2004; 18: 238–42.CrossRefGoogle ScholarPubMed
Camacho, E., Hernandez, L., Hernandez, S., et al.ATM gene inactivation in mantle cell lymphoma mainly occurs by truncating mutations and missense mutations involving the phosphatidylinositol-3 kinase domain and is associated with increasing numbers of chromosomal imbalances. Blood, 2002; 99: 238–44.CrossRefGoogle ScholarPubMed
Pettitt, A. R., Sherrington, P. D., Stewart, G., et al.p53 dysfunction in B-cell chronic lymphocytic leukemia: inactivation of ATM as an alternative to TP53 mutation. Blood, 2001; 98: 814–22.CrossRefGoogle ScholarPubMed
Gronbaek, K., Worm, J., Ralfkiaer, E., et al.ATM mutations are associated with inactivation of the ARF-TP53 tumor suppressor pathway in diffuse large B-cell lymphoma. Blood, 2002; 100: 1430–7.CrossRefGoogle ScholarPubMed
Irwin, M. S.Family feud in chemosensitivity: p73 and mutant p53. Cell Cycle, 2004; 3: 319–23.CrossRefGoogle Scholar
Irwin, M. S., Kondo, K., Marin, M. C., et al.Chemosensitivity linked to p73 function. Cancer Cell, 2003; 3: 403–10.CrossRefGoogle ScholarPubMed
Di Como, C. J., Gaiddon, C., & Prives, C.p73 function is inhibited by tumor-derived p53 mutants in mammalian cells. Mol Cell Biol, 1999; 19: 1438–49.CrossRefGoogle ScholarPubMed
Strano, S., Munarriz, E., Rossi, M., et al.Physical and functional interaction between p53 mutants and different isoforms of p73. J Biol Chem, 2000; 275: 29 503–12.CrossRefGoogle ScholarPubMed
Martinez-Delgado, B., Melendez, B., Cuadros, M., et al.Frequent inactivation of the p73 gene by abnormal methylation or LOH in non-Hodgkin's lymphomas. Int J Cancer, 2002; 102: 15–19.CrossRefGoogle ScholarPubMed
Leupin, N., Luthi, A., Novak, U., et al.P73 status in B-cell chronic lymphocytic leukaemia. Leuk Lymphoma, 2004; 45: 1205–7.CrossRefGoogle ScholarPubMed
Wang, M. L., Tuli, R., Manner, P. A., et al.Direct and indirect induction of apoptosis in human mesenchymal stem cells in response to titanium particles. J Orthop Res, 2003; 21: 697–707.CrossRefGoogle ScholarPubMed
Lane, D. P. & Hupp, T. R.Drug discovery and p53. Drug Discov Today, 2003; 8: 347–55.CrossRefGoogle ScholarPubMed
Zhang, W., Kornblau, S. M., Kobayashi, T., et al.High levels of constitutive WAF1/Cip1 protein are associated with chemo resistance in acute myelogenous leukemia. Clin Cancer Res, 1995; 1: 1051–7.Google Scholar
Steinman, R. A. & Johnson, D. E.p21WAF1 prevents down-modulation of the apoptotic inhibitor protein c-IAP1 and inhibits leukemic apoptosis. Mol Med, 2000; 6: 736–49.Google ScholarPubMed
Roman-Gomez, J., Castillejo, J. A., Jimenez, A., et al.5′ CpG island hypermethylation is associated with transcriptional silencing of the p21(CIP1/WAF1/SDI1) gene and confers poor prognosis in acute lymphoblastic leukemia. Blood, 2002; 99: 2291–6.CrossRefGoogle ScholarPubMed
Raveh, T., Droguett, G., Horwitz, M. S., DePinho, R. A., & Kimchi, A.DAP kinase activates a p19ARF/p53-mediated apoptotic checkpoint to suppress oncogenic transformation. Nat Cell Biol, 2001; 3: 1–7.CrossRefGoogle ScholarPubMed
Shohat, G., Spivak-Kroizman, T., Eisenstein, M., & Kimchi, A.The regulation of death-associated protein (DAP) kinase in apoptosis. Eur Cytokine Netw, 2002; 13: 398–400.Google ScholarPubMed
Ng, M. H.Death associated protein kinase: from regulation of apoptosis to tumor suppressive functions and B cell malignancies. Apoptosis, 2002; 7: 261–70.CrossRefGoogle ScholarPubMed
Katzenellenbogen, R. A., Baylin, S. B., & Herman, J. G.Hypermethylation of the DAP-kinase CpG island is a common alteration in B-cell malignancies. Blood, 1999; 93: 4347–53.Google ScholarPubMed
Shiramizu, B. & Mick, P.Epigenetic changes in the DAP-kinase CpG island in pediatric lymphoma. Med Pediatr Oncol, 2003; 41: 527–31.CrossRefGoogle ScholarPubMed
Galm, O., Wilop, S., Reichelt, J., et al.DNA methylation changes in multiple myeloma. Leukemia, 2004; 18: 1687–92.CrossRefGoogle ScholarPubMed
Nakatsuka, S., Takakuwa, T., Tomita, Y., et al.Hypermethylation of death-associated protein (DAP) kinase CpG island is frequent not only in B-cell but also in T- and natural killer (NK)/T-cell malignancies. Cancer Sci, 2003; 94: 87–91.CrossRefGoogle ScholarPubMed
Voso, M. T., Scardocci, A., Guidi, F., et al.Aberrant methylation of DAP-kinase in therapy-related acute myeloid leukemia and myelodysplastic syndromes. Blood, 2004; 103: 698–700.CrossRefGoogle ScholarPubMed
Cheok, M. H., Yang, W., Pui, C. H., et al.Treatment-specific changes in gene expression discriminate in vivo drug response in human leukemia cells. Nat Genet, 2003; 34: 85–90.CrossRefGoogle ScholarPubMed

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  • Apoptosis and chemoresistance
    • By Kirsteen H. Maclean, Research Fellow, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA, John L. Cleveland, Member, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA
  • Edited by Ching-Hon Pui
  • Book: Childhood Leukemias
  • Online publication: 01 July 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511471001.013
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  • Apoptosis and chemoresistance
    • By Kirsteen H. Maclean, Research Fellow, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA, John L. Cleveland, Member, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA
  • Edited by Ching-Hon Pui
  • Book: Childhood Leukemias
  • Online publication: 01 July 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511471001.013
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  • Apoptosis and chemoresistance
    • By Kirsteen H. Maclean, Research Fellow, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA, John L. Cleveland, Member, Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, TN, USA
  • Edited by Ching-Hon Pui
  • Book: Childhood Leukemias
  • Online publication: 01 July 2010
  • Chapter DOI: https://doi.org/10.1017/CBO9780511471001.013
Available formats
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