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15 - ALK: Anaplastic lymphoma kinase

from Part 2.1 - Molecular pathways underlying carcinogenesis: signal transduction

Published online by Cambridge University Press:  05 February 2015

By
Karen Pulford
Edited by
Edward P. Gelmann ,
Charles L. Sawyers  and
Frank J. Rauscher, III
Karen Pulford
Affiliation:
Nuield Division of Clinical Laboratory Sciences, Radclife Department of Medicine, University of Oxford, Oxford, UK
Edward P. Gelmann
Affiliation:
Columbia University, New York
Charles L. Sawyers
Affiliation:
Memorial Sloan-Kettering Cancer Center, New York
Frank J. Rauscher, III
Affiliation:
The Wistar Institute Cancer Centre, Philadelphia
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Summary

Introduction

Anaplastic lymphoma kinase, (also known as ALK, CD246 antigen, Ki 1 antigen, ALK tyrosine kinase receptor) is a member of the receptor tyrosine kinase (RTK) family. These proteins are essential for the transmission of extra-cellular signals to the interior of the cell and play essential roles in cellular activities including cell-cycle progression, differentiation, migration, reaction to stress, and survival.

ALK has been ascribed a role in neural development in humans, rodents, birds, Drosophila and Caenorhabditis elegans, as well as being necessary for gut muscle development in Drosophila. While many of the signaling pathways associated with ALK are common to other RTKs, the normal function of ALK has yet to be completely understood.

In common with other RTKs, ALK is frequently afected by chromosomal abnormalities, e.g. point mutations and translocations, resulting in the production of oncogenic ALK proteins with constitutively activated TK domains. Importantly, in contrast to other RTKs, oncogenic ALK proteins are present in hematopoietic as well as non-hematopoietic tumors. Indeed, the identiication of nucleophosmin (NPM)-ALK led to the recognition of the tumor entity ALK-positive anaplastic large cell lymphoma (ALCL). Much of the information concerning the signaling pathways of ALK has been elucidated from the study of the NPM-ALK fusion protein.

Type
Chapter
Information
Molecular Oncology
Causes of Cancer and Targets for Treatment
 , pp. 162 - 189
Publisher: Cambridge University Press
Print publication year: 2013

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References

Morris, SW, Kirstein, MN, Valentine, MB, et al. Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma. Science 1994;263:1281–4.CrossRef
Shiota, M, Fujimoto, J, Semba, T, et al. Hyperphosphorylation of a novel 80 kDa protein-tyrosine kinase similar to Ltk in a human Ki-1 lymphoma cell line, AMS3. Oncogene 1994;9:1567–74.
Morris, SW, Naeve, C, Mathew, P, et al. ALK, the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin's lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK). Oncogene 1997;14:2175–88.CrossRef
Iwahara, T, Fujimoto, J, Wen, D, et al. Molecular characterization of ALK, a receptor tyrosine kinase expressed specifically in the nervous system. Oncogene 1997;14:439–49.CrossRef
Loren, CE, Scully, A, Grabbe, C, et al. Identification and characterization of DAlk: a novel Drosophila melanogaster RTK which drives ERK activation in vivo. Genes and Cells 2001;6:531–44.CrossRef
Palmer, RH, Vernersson, E, Grabbe, C, Hallberg, B. Anaplastic lymphoma kinase: signalling in development and disease. Biochemical Journal 2009;420:345–61.CrossRef
Pulford, K, Morris, SW, Turturro, F.Anaplastic lymphoma kinase proteins in growth control and cancer. Journal of Cell Physiology 2004;199:330–58.CrossRefGoogle ScholarPubMed
Hubbard, SR. Crystal structure of the activated insulin receptor tyrosine kinase in complex with peptide substrate and ATP analog. EMBO Journal 1997;16:5572–81.CrossRef
Manning, G, Whyte, DB, Martinez, R, Hunter, T, Sudarsanam S. The protein kinase complement of the human genome. Science 2002;298:1912–34.CrossRef
Robinson, DR, Wu, YM, Lin, SF. The protein tyrosine kinase family of the human genome. Oncogene 2000;19:5548–57.CrossRef
Stoica, GE, Kuo, A, Aigner, A, et al. Identification of anaplastic lymphoma kinase as a receptor for the growth factor pleiotrophin. Journal of Biological Chemistry 2001;276:16 772–9.CrossRefGoogle ScholarPubMed
Stoica, GE, Kuo, A, Powers, C, et al. Midkine binds to anaplastic lymphoma kinase (ALK) and acts as a growth factor for different cell types. Journal of Biological Chemistry 2002;277:35 990–8.CrossRefGoogle ScholarPubMed
Loren, CE, Englund, C, Grabbe, C, et al. A crucial role for the anaplastic lymphoma kinase receptor tyrosine kinase in gut development in Drosophila melanogaster. EMBO Report 2003;4:781–6.CrossRef
Beckmann, G, Bork, P. An adhesive domain detected in functionally diverse receptors. Trends in Biochemical Sciences 1993;18:40–1.CrossRef
Fass, D, Blacklow, S, Kim, PS, Berger, JM. Molecular basis of familial hypercholesterolaemia from structure of LDL receptor module. Nature 1997;388:691–3.CrossRef
Li, E, Hristova, K. Role of receptor tyrosine kinase transmembrane domains in cell signaling and human pathologies. Biochemistry 2006;45:6241–51.CrossRef
Bossi, RT, Saccardo, MB, Ardini, E, et al. Crystal structures of anaplastic lymphoma kinase in complex with ATP competitive inhibitors. Biochemistry 2010;49:6813–25.CrossRef
Donella-Deana, A, Marin, O, Cesaro, L, et al. Unique substrate specificity of anaplastic lymphoma kinase (ALK):development of phosphoacceptor peptides for the assay of ALK activity. Biochemistry 2005;44:8533–42.CrossRef
Tartari, CJ, Gunby, RH, Coluccia, AM, et al. Characterization of some molecular mechanisms governing autoactivation of the catalytic domain of the anaplastic lymphoma kinase. Journal of Biological Chemistry 2008;283:3743–50.CrossRefGoogle ScholarPubMed
Lee, CC, Jia, Y, Li, N, et al. Crystal structure of the ALK (anaplastic lymphoma kinase) catalytic domain. Biochemical Journal 2010;430:425–37.CrossRef
Pulford, K, Lamant, L, Morris, SW, et al. Detection of anaplastic lymphoma kinase (ALK) and nucleolar protein nucleophosmin (NPM)-ALK proteins in normal and neoplastic cells with the monoclonal antibody ALK1. Blood 1997;89:1394–404.
Vernersson, E, Khoo, NK, Henriksson, ML, et al. Characterization of the expression of the ALK receptor tyrosine kinase in mice. Gene Expression Patterns 2006;6:448–61.CrossRef
Englund, C, Loren, CE, Grabbe, C, et al. Jeb signals through the Alk receptor tyrosine kinase to drive visceral muscle fusion. Nature 2003;425:512–16.CrossRef
Lee, HH, Norris, A, Weiss, JB, Frasch, M. Jelly belly protein activates the receptor tyrosine kinase Alk to specify visceral muscle pioneers. Nature 2003;425:507–12.CrossRef
Bilsland, JG, Wheeldon, A, Mead, A, et al. Behavioral and neurochemical alterations in mice deficient in anaplastic lymphoma kinase suggest therapeutic potential for psychiatric indications. Neuropsychopharmacology 2008;33:685–700.CrossRef
Weiss, JB, Xue, C, Benice, T, et al. Anaplastic lymphoma kinase and leukocyte tyrosine kinase:functions and genetic interactions in learning, memory and adult neurogenesis. Pharmacology, Biochemistry and Behavior 2012;100:566–74.CrossRef
Liao, EH, Hung, W, Abrams, B, Zhen, M. An SCF-like ubiquitin ligase complex that controls presynaptic differentiation. Nature 2004;430:345–50.CrossRef
Shinkai, Y, Yamamoto, Y, Fujiwara, M, et al. Behavioral choice between conflicting alternatives is regulated by a receptor guanylyl cyclase, GCY-28, and a receptor tyrosine kinase, SCD-2, in AIA interneurons of Caenorhabditis elegans. Journal of Neuroscience 2011;31:3007–15.CrossRefGoogle Scholar
Cheng, LY, Bailey, AP, Leevers, SJ, et al. Anaplastic lymphoma kinase spares organ growth during nutrient restriction in Drosophila. Cell 2011;146:435–47.CrossRef
Rohrbough, J, Kent, KS, Broadie, K, Weiss, JB. Jelly belly trans-synaptic signaling to anaplastic lymphoma kinase regulates neurotransmission strength and synapse architecture. Developmental Neurobiology 2012;73:189–208.CrossRef
Shirinian, M, Varshney, G, Loren, CE, Grabbe, C, Palmer, RH. Drosophila anaplastic lymphoma kinase regulates Dpp signalling in the developing embryonic gut. Differentiation 2007;75:418–26.CrossRef
Gouzi, JY, Moressis, A, Walker, JA, et al. The receptor tyrosine kinase Alk controls neurofibromin functions in Drosophila growth and learning. PLoS Genetics 2011;7:e1002281.
Hurley, SP, Clary, DO, Copie, V, Lefcort, F.Anaplastic lymphoma kinase is dynamically expressed on subsets of motor neurons and in the peripheral nervous system. Journal of Comparative Neurology 2006;495:202–12.CrossRefGoogle ScholarPubMed
Bazigou, E, Apitz, H, Johansson, J, et al. Anterograde Jelly belly and Alk receptor tyrosine kinase signaling mediates retinal axon targeting in Drosophila. Cell 2007;128:961–75.CrossRef
Chikamori, M, Fujimoto, J, Tokai-Nishizumi, N, Yamamoto, T. Identification of multiple SNT-binding sites on NPM-ALK oncoprotein and their involvement in cell transformation. Oncogene 2007;26:2950–4.CrossRef
Bai, RY, Dieter, P, Peschel, C, Morris, SW, Duyster, J. Nucleophosmin-anaplastic lymphoma kinase of large-cell anaplastic lymphoma is a constitutively active tyrosine kinase that utilizes phospholipase C-gamma to mediate its mitogenicity. Molecular and Cellular Biology 1998;18:6951–61.CrossRef
Mourali, J, Benard, A, Lourenco, FC, et al. Anaplastic lymphoma kinase is a dependence receptor whose proapoptotic functions are activated by caspase cleavage. Molecular and Cellular Biology 2006;26:6209–22.CrossRef
Allouche, M. ALK is a novel dependence receptor: potential implications in development and cancer. Cell Cycle 2007;6:1533–8.CrossRef
Cessna, MH, Zhou, H, Sanger, WG, et al. Expression of ALK1 and p80 in inflammatory myofibroblastic tumor and its mesenchymal mimics:a study of 135 cases. Modern Pathology 2002;15:931–8.CrossRef
Pillay, K, Govender, D, Chetty, R. ALK protein expression in rhabdomyosarcomas. Histopathology 2002;41:461–7.CrossRef
Lamant, L, Pulford, K, Bischof, D, et al. Expression of the ALK tyrosine kinase gene in neuroblastoma. American Journal of Pathology 2000;156:1711–21.CrossRefGoogle ScholarPubMed
Powers, C, Aigner, A, Stoica, GE, McDonnell, K, Wellstein, A.Pleiotrophin signaling through anaplastic lymphoma kinase is rate-limiting for glioblastoma growth. Journal of Biological Chemistry 2002;277:14 153–8.CrossRefGoogle ScholarPubMed
Webb, TR, Slavish, J, George, RE, et al. Anaplastic lymphoma kinase: role in cancer pathogenesis and small-molecule inhibitor development for therapy. Expert Reviews in Anticancer Therapy 2009;9:331–56.CrossRef
Rikova, K, Guo, A, Zeng, Q, et al. Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer. Cell 2007;131:1190–203.CrossRef
Miyake, I, Hakomori, Y, Shinohara, A, et al. Activation of anaplastic lymphoma kinase is responsible for hyperphosphorylation of ShcC in neuroblastoma cell lines. Oncogene 2002;21:5823–34.CrossRef
Dirks, WG, Fahnrich, S, Lis, Y, et al. Expression and functional analysis of the anaplastic lymphoma kinase (ALK) gene in tumor cell lines. International Journal of Cancer 2002;100:49–56.CrossRefGoogle ScholarPubMed
Mosse, YP, Laudenslager, M, Longo, L, et al. Identification of ALK as a major familial neuroblastoma predisposition gene. Nature 2008;455:930–5.CrossRef
Subramaniam, MM, Piqueras, M, Navarro, S, Noguera, R. Aberrant copy numbers of ALK gene is a frequent genetic alteration in neuroblastomas. Human Pathology 2009;40:1638–42.CrossRef
Van Roy, N, De Preter, K, Hoebeeck, J, et al. The emerging molecular pathogenesis of neuroblastoma:implications for improved risk assessment and targeted therapy. Genome Medicine 2009;1:74.CrossRef
Janoueix-Lerosey, I, Lequin, D, Brugieres, L, et al. Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma. Nature 2008;455:967–70.CrossRef
Shiota, M, Mori, S. The clinicopathological features of anaplastic large cell lymphomas expressing p80NPM/ALK. Leukemia and Lymphoma 1996;23:25–32.CrossRef
Shiota, M, Mori, S. Anaplastic large cell lymphomas expressing the novel chimeric protein p80NPM/ALK:a distinct clinicopathologic entity. Leukemia 1997;11 Suppl 3:538–40.
Benharroch, D, Meguerian-Bedoyan, Z, Lamant, L, et al. ALK-positive lymphoma:a single disease with a broad spectrum of morphology. Blood 1998;91:2076–84.
Onciu, M, Behm, FG, Downing, JR, et al. ALK-positive plasmablastic B-cell lymphoma with expression of the NPM-ALK fusion transcript: report of 2 cases. Blood 2003;102:2642–4.CrossRef
Lamant, L, Dastugue, N, Pulford, K, Delsol, G, Mariame, B. A new fusion gene TPM3-ALK in anaplastic large cell lymphoma created by a (1;2)(q25;p23) translocation. Blood 1999;93:3088–95.
Siebert, R, Gesk, S, Harder, L, et al. Complex variant translocation t(1;2) with TPM3-ALK fusion due to cryptic ALK gene rearrangement in anaplastic large-cell lymphoma. Blood 1999;94:3614–17.
Lawrence, B, Perez-Atayde, A, Hibbard, MK, et al. TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors. American Journal of Pathology 2000;157:377–84.CrossRefGoogle ScholarPubMed
Sugawara, E, Togashi, Y, Kuroda, N, et al. Identification of anaplastic lymphoma kinase fusions in renal cancer:large-scale immunohistochemical screening by the intercalated antibody-enhanced polymer method. Cancer 2012;118:4427–36.CrossRef
Hernandez, L, Pinyol, M, Hernandez, S, et al. TRK-fused gene (TFG) is a new partner of ALK in anaplastic large cell lymphoma producing two structurally different TFG-ALK translocations. Blood 1999;94:3265–8.
Hernandez, L, Bea, S, Bellosillo, B, et al. Diversity of genomic breakpoints in TFG-ALK translocations in anaplastic large cell lymphomas:identification of a new TFG-ALK(XL) chimeric gene with transforming activity. American Journal of Pathology 2002;160:1487–94.CrossRefGoogle ScholarPubMed
Ma, Z, Cools, J, Marynen, P, et al. Inv(2)(p23q35) in anaplastic large-cell lymphoma induces constitutive anaplastic lymphoma kinase (ALK) tyrosine kinase activation by fusion to ATIC, an enzyme involved in purine nucleotide biosynthesis. Blood 2000;95:2144–9.
Trinei, M, Lanfrancone, L, Campo, E, et al. A new variant anaplastic lymphoma kinase (ALK)-fusion protein (ATIC-ALK) in a case of ALK-positive anaplastic large cell lymphoma. Cancer Research 2000;60:793–8.
Debiec-Rychter, M, Marynen, P, Hagemeijer, A, Pauwels, P. ALK-ATIC fusion in urinary bladder inflammatory myofibroblastic tumor. Genes Chromosomes and Cancer 2003;38:187–90.CrossRef
Touriol, C, Greenland, C, Lamant, L, et al. Further demonstration of the diversity of chromosomal changes involving 2p23 in ALK-positive lymphoma:2 cases expressing ALK kinase fused to CLTCL (clathrin chain polypeptide-like). Blood 2000;95:3204–7.
Bridge, JA, Kanamori, M, Ma, Z, et al. Fusion of the ALK gene to the clathrin heavy chain gene, CLTC, in inflammatory myofibroblastic tumor. American Journal of Pathology 2001;159:411–15.CrossRefGoogle ScholarPubMed
De Paepe, P, Baens, M, van Krieken, H, et al. ALK activation by the CLTC-ALK fusion is a recurrent event in large B-cell lymphoma. Blood 2003;102:2638–41.CrossRef
Zhang, D, Denley, RC, Filippa, DA, Teruya-Feldstein, J. ALK-positive diffuse large B-cell lymphoma with the t(2;17)(p23;q23). Applied Immunohistochemistry and Molecular Morphology 2009;17:172–7.CrossRef
Patel, AS, Murphy, KM, Hawkins, AL, et al. RANBP2 and CLTC are involved in ALK rearrangements in inflammatory myofibroblastic tumors. Cancer Genetics and Cytogenetics 2007;176:107–14.CrossRef
Tort, F, Campo, E, Pohlman, B, Hsi, E. Heterogeneity of genomic breakpoints in MSN-ALK translocations in anaplastic large cell lymphoma. Human Pathology 2004;35:1038–41.CrossRef
Tort, F, Pinyol, M, Pulford, K, et al. Molecular characterization of a new ALK translocation involving moesin (MSN-ALK) in anaplastic large cell lymphoma. Laboratory Investigation 2001;81:419–26.CrossRef
Hisaoka, M, Shimajiri, S, Matsuki, Y, et al. Inflammatory myofibroblastic tumor with predominant anaplastic lymphoma kinase-positive cells lacking a myofibroblastic phenotype. Pathology International 2003;53:376–81.CrossRef
Du, XL, Hu, H, Lin, DC, et al. Proteomic profiling of proteins dysregulated in Chinese esophageal squamous cell carcinoma. Journal of Molecular Medicine 2007;85:863–75.CrossRefGoogle ScholarPubMed
Jazii, FR, Najafi, Z, Malekzadeh, R, et al. Identification of squamous cell carcinoma associated proteins by proteomics and loss of beta tropomyosin expression in esophageal cancer. World Journal of Gastroenterology 2006;12:7104–12.CrossRefGoogle ScholarPubMed
Cools, J, Wlodarska, I, Somers, R, et al. Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor. Genes Chromosomes and Cancer 2002;34:354–62.CrossRef
Ma, Z, Hill, DA, Collins, MH, et al. Fusion of ALK to the Ran-binding protein 2 (RANBP2) gene in inflammatory myofibroblastic tumor. Genes Chromosomes and Cancer 2003;37:98–105.CrossRef
Marino-Enriquez, A, Wang, WL, Roy, A, et al. Epithelioid inflammatory myofibroblastic sarcoma: An aggressive intra-abdominal variant of inflammatory myofibroblastic tumor with nuclear membrane or perinuclear ALK. American Journal of Surgical Pathology;35:135–44.CrossRef
Lamant, L, Gascoyne, RD, Duplantier, MM, et al. Non-muscle myosin heavy chain (MYH9):a new partner fused to ALK in anaplastic large cell lymphoma. Genes Chromosomes and Cancer 2003;37:427–32.CrossRef
Debelenko, LV, Arthur, DC, Pack, SD, et al. Identification of CARS-ALK fusion in primary and metastatic lesions of an inflammatory myofibroblastic tumor. Laboratory Investigation 2003;83:1255–65.CrossRef
Panagopoulos, I, Nilsson, T, Domanski, HA, et al. Fusion of the SEC31L1 and ALK genes in an inflammatory myofibroblastic tumor. International Journal of Cancer 2006;118:1181–6.CrossRefGoogle Scholar
Van Roosbroeck, K, Cools, J, Dierickx, D, et al. ALK-positive large B-cell lymphomas with cryptic SEC31A-ALK and NPM1-ALK fusions. Haematologica;95:509–13.
Bedwell, C, Rowe, D, Moulton, D, et al. Cytogenetically complex SEC31A-ALK fusions are recurrent in ALK-positive large B-cell lymphomas. Haematologica 2011;96:343–6.CrossRef
Soda, M, Choi, YL, Enomoto, M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007;448:561–6.CrossRef
Choi, YL, Takeuchi, K, Soda, M, et al. Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer. Cancer Research 2008;68:4971–6.CrossRef
Perner, S, Wagner, PL, Demichelis, F, et al. EML4-ALK fusion lung cancer: a rare acquired event. Neoplasia 2008;10:298–302.CrossRef
Shinmura, K, Kageyama, S, Tao, H, et al. EML4-ALK fusion transcripts, but no NPM-, TPM3-, CLTC-, ATIC-, or TFG-ALK fusion transcripts, in non-small cell lung carcinomas. Lung Cancer 2008;61:163–9.CrossRef
Lin, E, Li, L, Guan, Y, et al. Exon array profiling detects EML4-ALK fusion in breast, colorectal, and non-small cell lung cancers. Molecular Cancer Research 2009;7:1466–76.CrossRef
Takeuchi, K, Choi, YL, Togashi, Y, et al. KIF5B-ALK, a novel fusion oncokinase identified by an immunohistochemistry-based diagnostic system for ALK-positive lung cancer. Clinical Cancer Research 2009;15:3143–9.CrossRef
Wong, DW, Leung, EL, Wong, SK, et al. A novel KIF5B-ALK variant in nonsmall cell lung cancer. Cancer 2011;117:2709–18.CrossRef
Takeuchi, K, Soda, M, Togashi, Y, et al. Identification of a novel fusion, SQSTM1-ALK, in ALK-positive large B-cell lymphoma. Haematologica 2011;96:464–7.CrossRef
Debelenko, LV, Raimondi, SC, Daw, N, et al. Renal cell carcinoma with novel VCL-ALK fusion: new representative of ALK-associated tumor spectrum. Modern Pathology 2010;24:430–42.CrossRef
Togashi, Y, Soda, M, Sakata, S, et al. KLC1-ALK: a novel fusion in lung cancer identified using a formalin-fixed paraffin-embedded tissue only. PLoS One 2012;7:e31323.
Jung, Y, Kim, P, Keum, J, et al. Discovery of ALK-PTPN3 gene fusion from human non-small cell lung carcinoma cell line using next generation RNA sequencing. Genes Chromosomes and Cancer 2012;51:590–7.CrossRef
Lipson, D, Capelletti, M, Yelensky, R, et al. Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies. Nature Medicine 2012;18:382–4.CrossRef
Ren, H, Tan, ZP, Zhu, X, et al. Identification of anaplastic lymphoma kinase as a potential therapeutic target in ovarian cancer. Cancer Research 2012;72:3312–23.CrossRef
Takeuchi, K, Soda, M, Togashi, Y, et al. Pulmonary inflammatory myofibroblastic tumor expressing a novel fusion, PPFIBP1-ALK:reappraisal of anti-ALK immunohistochemistry as a tool for novel ALK fusion identification. Clinical Cancer Research 2011;17:3341–8.CrossRef
Stachurski, D, Miron, PM, Al-Homsi, S, et al. Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma with a complex karyotype and cryptic 3ʹ ALK gene insertion to chromosome 4 q22–24. Human Pathology 2007;38:940–5.CrossRef
Liang, X, Meech, SJ, Odom, LF, et al. Assessment of t(2;5)(p23;q35) translocation and variants in pediatric ALK+ anaplastic large cell lymphoma. American Journal of Clinical Pathology 2004;121:496–506.CrossRefGoogle Scholar
Chiarle, R, Voena, C, Ambrogio, C, Piva, R, Inghirami, G. The anaplastic lymphoma kinase in the pathogenesis of cancer. Nature Reviews Cancer 2008;8:11–23.CrossRef
Kuo, AH, Stoica, GE, Riegel, AT, Wellstein, A. Recruitment of insulin receptor substrate-1 and activation of NF-kappaB essential for midkine growth signaling through anaplastic lymphoma kinase. Oncogene 2007;26:859–69.CrossRef
Wellstein, A. ALK receptor activation, ligands and therapeutic targeting in glioblastoma and in other cancers. Frontiers in Oncology 2012;2:192.CrossRef
Reiff, T, Huber, L, Kramer, M, et al. Midkine and Alk signaling in sympathetic neuron proliferation and neuroblastoma predisposition. Development 2011;138:4699–708.CrossRef
Grzelinski, M, Bader, N, Czubayko, F, Aigner, A.Ribozyme-targeting reveals the rate-limiting role of pleiotrophin in glioblastoma. International Journal of Cancer 2005;117:942–51.CrossRefGoogle ScholarPubMed
Stylianou, DC, Auf der Maur, A, Kodack, DP, et al. Effect of single-chain antibody targeting of the ligand-binding domain in the anaplastic lymphoma kinase receptor. Oncogene 2009;28:3296–306.CrossRef
Bowden, ET, Stoica, GE, Wellstein, A.Anti-apoptotic signaling of pleiotrophin through its receptor, anaplastic lymphoma kinase. Journal of Biological Chemistry 2002;277:35 862–8.CrossRefGoogle ScholarPubMed
Grzelinski, M, Steinberg, F, Martens, T, et al. Enhanced antitumorigenic effects in glioblastoma on double targeting of pleiotrophin and its receptor ALK. Neoplasia 2009;11:145–56.CrossRef
Mi, R, Chen, W, Hoke, A. Pleiotrophin is a neurotrophic factor for spinal motor neurons. Proceedings of the National Academy of Sciences USA 2007;104:4664–9.CrossRef
Yanagisawa, H, Komuta, Y, Kawano, H, Toyoda, M, Sango, K. Pleiotrophin induces neurite outgrowth and up-regulates growth-associated protein (GAP)-43 mRNA through the ALK/GSK3beta/beta-catenin signaling in developing mouse neurons. Neuroscience Research 2009;66:111–16.CrossRef
Moog-Lutz, C, Degoutin, J, Gouzi, JY, et al. Activation and inhibition of anaplastic lymphoma kinase receptor tyrosine kinase by monoclonal antibodies and absence of agonist activity of pleiotrophin. Journal of Biological Chemistry 2005;280:26 039–48.CrossRefGoogle ScholarPubMed
Maeda, N, Nishiwaki, T, Shintani, T, Hamanaka, H, Noda, M.6B4 proteoglycan/phosphacan, an extracellular variant of receptor-like protein-tyrosine phosphatase zeta/RPTPbeta, binds pleiotrophin/heparin-binding growth-associated molecule (HB-GAM). Journal of Biological Chemistry 1996;271:21 446–52.CrossRefGoogle Scholar
Meng, K, Rodriguez-Pena, A, Dimitrov, T, et al. Pleiotrophin signals increased tyrosine phosphorylation of beta beta-catenin through inactivation of the intrinsic catalytic activity of the receptor-type protein tyrosine phosphatase beta/zeta. Proceedings of the National Academy of Sciences USA 2000;97:2603–8.CrossRef
Raulo, E, Julkunen, I, Merenmies, J, Pihlaskari, R, Rauvala, H.Secretion and biological activities of heparin-binding growth-associated molecule. Neurite outgrowth-promoting and mitogenic actions of the recombinant and tissue-derived protein. Journal of Biological Chemistry 1992;267:11 408–16.Google ScholarPubMed
Maeda, N, Ichihara-Tanaka, K, Kimura, T, et al. A receptor-like protein-tyrosine phosphatase PTPzeta/RPTPbeta binds a heparin-binding growth factor midkine. Involvement of arginine 78 of midkine in the high affinity binding to PTPzeta. Journal of Biological Chemistry 1999;274:12 474–9.CrossRefGoogle ScholarPubMed
Muramatsu, H, Zou, K, Sakaguchi, N, et al. LDL receptor-related protein as a component of the midkine receptor. Biochemical and Biophysical Research Communications 2000;270:936–41.CrossRef
Muramatsu, H, Zou, P, Suzuki, H, et al. alpha4beta1- and alpha6beta1-integrins are functional receptors for midkine, a heparin-binding growth factor. Journal of Cell Science 2004;117:5405–15.CrossRefGoogle ScholarPubMed
Perez-Pinera, P, Zhang, W, Chang, Y, Vega, JA, Deuel, TF.Anaplastic lymphoma kinase is activated through the pleiotrophin/receptor protein-tyrosine phosphatase beta/zeta signaling pathway:an alternative mechanism of receptor tyrosine kinase activation. Journal of Biological Chemistry 2007;282:28 683–90.CrossRefGoogle ScholarPubMed
Lu, KV, Jong, KA, Kim, GY, et al. Differential induction of glioblastoma migration and growth by two forms of pleiotrophin. Journal of Biological Chemistry 2005;280:26 953–64.CrossRefGoogle ScholarPubMed
Mathivet, T, Mazot, P, Vigny, M. In contrast to agonist monoclonal antibodies, both C-terminal truncated form and full length form of Pleiotrophin failed to activate vertebrate ALK (anaplastic lymphoma kinase)? Cellular Signaling 2007;19:2434–43.
Englund, C, Birve, A, Falileeva, L, Grabbe, C, Palmer, RH. Miple1 and miple2 encode a family of MK/PTN homologues in Drosophila melanogaster. Development, Genes and Evolution 2006;216:10–18.CrossRef
Ishihara, T, Iino, Y, Mohri, A, et al. HEN-1, a secretory protein with an LDL receptor motif, regulates sensory integration and learning in Caenorhabditis elegans. Cell 2002;109:639–49.CrossRef
Yang, HL, Eriksson, T, Vernersson, E, et al. The ligand Jelly Belly (Jeb) activates the Drosophila Alk RTK to drive PC12 cell differentiation, but is unable to activate the mouse ALK RTK. Journal of Experimental Zoology B Molecular and Developmental Evolution 2007;308:269–82.CrossRefGoogle ScholarPubMed
Stute, C, Schimmelpfeng, K, Renkawitz-Pohl, R, Palmer, RH, Holz, A. Myoblast determination in the somatic and visceral mesoderm depends on Notch signalling as well as on milliways(mili(Alk)) as receptor for Jeb signalling. Development 2004;131:743–54.CrossRef
Souttou, B, Carvalho, NB, Raulais, D, Vigny, M.Activation of anaplastic lymphoma kinase receptor tyrosine kinase induces neuronal differentiation through the mitogen-activated protein kinase pathway. Journal of Biological Chemistry 2001;276:9526–31.CrossRefGoogle ScholarPubMed
Degoutin, J, Vigny, M, Gouzi, JY. ALK activation induces Shc and FRS2 recruitment: Signaling and phenotypic outcomes in PC12 cells differentiation. FEBS Letters 2007;581:727–34.CrossRef
Caren, H, Abel, F, Kogner, P, Martinsson, T. High incidence of DNA mutations and gene amplifications of the ALK gene in advanced sporadic neuroblastoma tumours. Biochemical Journal 2008;416:153–9.CrossRef
Chen, Y, Takita, J, Choi, YL, et al. Oncogenic mutations of ALK kinase in neuroblastoma. Nature 2008;455:971–4.CrossRef
George, RE, Sanda, T, Hanna, M, et al. Activating mutations in ALK provide a therapeutic target in neuroblastoma. Nature 2008;455:975–8.CrossRef
Passoni, L, Longo, L, Collini, P, et al. Mutation-independent anaplastic lymphoma kinase overexpression in poor prognosis neuroblastoma patients. Cancer Research 2009;69:7338–46.CrossRef
Cazes, A, Louis-Brennetot, C, Mazot, P, et al. Characterization of rearrangements involving the ALK gene reveals a novel truncated form associated with tumor aggressiveness in neuroblastoma. Cancer Research 2012;73:195–204.CrossRef
Osajima-Hakomori, Y, Miyake, I, Ohira, M, et al. Biological role of anaplastic lymphoma kinase in neuroblastoma. American Journal of Pathology 2005;167:213–22.CrossRefGoogle ScholarPubMed
Schonherr, C, Ruuth, K, Kamaraj, S, et al. Anaplastic Lymphoma Kinase (ALK) regulates initiation of transcription of MYCN in neuroblastoma cells. Oncogene 2012;31:5193–200.CrossRef
Bai, RY, Ouyang, T, Miething, C, et al. Nucleophosmin-anaplastic lymphoma kinase associated with anaplastic large-cell lymphoma activates the phosphatidylinositol 3-kinase/Akt antiapoptotic signaling pathway. Blood 2000;96:4319–27.
Slupianek, A, Nieborowska-Skorska, M, Hoser, G, et al. Role of phosphatidylinositol 3-kinase-Akt pathway in nucleophosmin/anaplastic lymphoma kinase-mediated lymphomagenesis. Cancer Research 2001;61:2194–9.
Motegi, A, Fujimoto, J, Kotani, M, Sakuraba, H, Yamamoto, T.ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth. Journal of Cell Science 2004;117:3319–29.CrossRefGoogle ScholarPubMed
Zamo, A, Chiarle, R, Piva, R, et al. Anaplastic lymphoma kinase (ALK) activates Stat3 and protects hematopoietic cells from cell death. Oncogene 2002;21:1038–47.CrossRef
Zhang, Q, Raghunath, PN, Xue, L, et al. Multilevel dysregulation of STAT3 activation in anaplastic lymphoma kinase-positive T/null-cell lymphoma. Journal of Immunology 2002;168:466–74.CrossRefGoogle ScholarPubMed
Amin, HM, Lin, Q, Lai, R. Jak3 contributes to the activation of ALK and Stat3 in ALK(+) anaplastic large cell lymphoma. Laboratory Investigation 2006;86:417–19;author reply 420–1.
Amin, HM, McDonnell, TJ, Ma, Y, et al. Selective inhibition of STAT3 induces apoptosis and G(1) cell cycle arrest in ALK-positive anaplastic large cell lymphoma. Oncogene 2004;23:5426–34.CrossRef
Nieborowska-Skorska, M, Slupianek, A, Xue, L, et al. Role of signal transducer and activator of transcription 5 in nucleophosmin/ anaplastic lymphoma kinase-mediated malignant transformation of lymphoid cells. Cancer Research 2001;61:6517–23.
Cussac, D, Greenland, C, Roche, S, et al. Nucleophosmin-anaplastic lymphoma kinase of anaplastic large-cell lymphoma recruits, activates, and uses pp60c-src to mediate its mitogenicity. Blood 2004;103:1464–71.CrossRef
Crockett, DK, Lin, Z, Elenitoba-Johnson, KS, Lim, MS. Identification of NPM-ALK interacting proteins by tandem mass spectrometry. Oncogene 2004;23:2617–29.CrossRef
Lim, MS, Elenitoba-Johnson, KS. Mass spectrometry-based proteomic studies of human anaplastic large cell lymphoma. Molecular and Cell Proteomics 2006;5:1787–98.CrossRef
Elenitoba-Johnson, KS, Crockett, DK, Schumacher, JA, et al. Proteomic identification of oncogenic chromosomal translocation partners encoding chimeric anaplastic lymphoma kinase fusion proteins. Proceedings of the National Academy of Sciences USA 2006;103:7402–7.CrossRef
Lim, MS, Carlson, ML, Crockett, DK, et al. The proteomic signature of NPM/ALK reveals deregulation of multiple cellular pathways. Blood 2009;114:1585–95.CrossRef
Cussac, D, Pichereaux, C, Colomba, A, et al. Proteomic analysis of anaplastic lymphoma cell lines: identification of potential tumour markers. Proteomics 2006;6:3210–22.CrossRef
Sjostrom, C, Seiler, C, Crockett, DK, et al. Global proteome profiling of NPM/ALK-positive anaplastic large cell lymphoma. Experimental Hematology 2007;35:1240–8.CrossRef
Bohling, SD, Jenson, SD, Crockett, DK, et al. Analysis of gene expression profile of TPM3-ALK positive anaplastic large cell lymphoma reveals overlapping and unique patterns with that of NPM-ALK positive anaplastic large cell lymphoma. Leukemia Research 2008;32:383–93.CrossRef
Wu, F, Wang, P, Young, LC, Lai, R, Li, L.Proteome-wide identification of novel binding partners to the oncogenic fusion gene protein, NPM-ALK, using tandem affinity purification and mass spectrometry. American Journal of Pathology 2009;174:361–70.CrossRefGoogle ScholarPubMed
Amin, HM, Lai, R. Pathobiology of ALK+ anaplastic large-cell lymphoma. Blood 2007;110:2259–67.CrossRef
Li, R, Morris, SW. Development of anaplastic lymphoma kinase (ALK) small-molecule inhibitors for cancer therapy. Medicinal Research Reviews 2008;28:372–412.CrossRef
Mosse, YP, Wood, A, Maris, JM. Inhibition of ALK signaling for cancer therapy. Clinical Cancer Research 2009;15:5609–14.CrossRef
Wasik, MA, Zhang, Q, Marzec, M, et al. Anaplastic lymphoma kinase (ALK)-induced malignancies: novel mechanisms of cell transformation and potential therapeutic approaches. Seminars in Oncology 2009;36:S27–35.
Riera, L, Lasorsa, E, Ambrogio, C, et al. Involvement of Grb2 adaptor protein in nucleophosmin-anaplastic lymphoma kinase (NPM-ALK)-mediated signaling and anaplastic large cell lymphoma growth. Journal of Biological Chemistry 2010;285:26 441–50.CrossRefGoogle ScholarPubMed
Pearson, JD, Lee, JK, Bacani, JT, Lai, R, Ingham, RJ.NPM-ALK and the JunB transcription factor regulate the expression of cytotoxic molecules in ALK-positive, anaplastic large cell lymphoma. International Journal of Clinical and Experimental Pathology 2011;4:124–33.Google ScholarPubMed
Armstrong, F, Duplantier, MM, Trempat, P, et al. Differential effects of X-ALK fusion proteins on proliferation, transformation, and invasion properties of NIH3T3 cells. Oncogene 2004;23:6071–82.CrossRef
Armstrong, F, Lamant, L, Hieblot, C, Delsol, G, Touriol, C.TPM3-ALK expression induces changes in cytoskeleton organisation and confers higher metastatic capacities than other ALK fusion proteins. European Journal of Cancer 2007;43:640–6.CrossRefGoogle ScholarPubMed
Rassidakis, GZ, Thomaides, A, Wang, S, et al. p53 gene mutations are uncommon but p53 is commonly expressed in anaplastic large-cell lymphoma. Leukemia 2005;19:1663–9.CrossRef
Cui, YX, Kerby, A, McDuff, FK, Ye, H, Turner, SD. NPM-ALK inhibits the p53 tumor suppressor pathway in an MDM2 and JNK-dependent manner. Blood 2009;113:5217–27.CrossRef
Yamamoto, H, Oda, Y, Saito, T, et al. p53 Mutation and MDM2 amplification in inflammatory myofibroblastic tumours. Histopathology 2003;42:431–9.CrossRef
Gelebart, P, Hegazy, SA, Wang, P, et al. Aberrant expression and biological significance of Sox2, an embryonic stem cell transcriptional factor, in ALK-positive anaplastic large cell lymphoma. Blood Cancer Journal 2012;2:e82.
Kasprzycka, M, Marzec, M, Liu, X, Zhang, Q, Wasik, MA. Nucleophosmin/anaplastic lymphoma kinase (NPM/ALK) oncoprotein induces the T regulatory cell phenotype by activating STAT3. Proceedings of the National Academy of Sciences USA 2006;103:9964–9.CrossRef
Roncador, G, Garcia, JF, Maestre, L, et al. FOXP3, a selective marker for a subset of adult T-cell leukaemia/lymphoma. Leukemia 2005;19:2247–53.CrossRef
Gjerdrum, LM, Woetmann, A, Odum, N, et al. FOXP3 positive regulatory T cells in cutaneous and systemic CD30 positive T-cell lymphoproliferations. European Journal of Haematology 2008;80:483–9.CrossRefGoogle ScholarPubMed
Bonzheim, I, Geissinger, E, Tinguely, M, et al. Evaluation of FoxP3 expression in peripheral T-cell lymphoma. American Journal of Clinical Pathology 2008;130:613–19.CrossRefGoogle ScholarPubMed
Marzec, M, Zhang, Q, Goradia, A, et al. Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1). Proceedings of the National Academy of Sciences USA 2008;105:20 852–7.
Keir, ME, Butte, MJ, Freeman, GJ, Sharpe, AH. PD-1 and its ligands in tolerance and immunity. Annual Review of Immunology 2008;26:677–704.CrossRef
Ambrogio, C, Martinengo, C, Voena, C, et al. NPM-ALK oncogenic tyrosine kinase controls T-cell identity by transcriptional regulation and epigenetic silencing in lymphoma cells. Cancer Research 2009;69:8611–19.CrossRef
Greenland, C, Touriol, C, Chevillard, G, et al. Expression of the oncogenic NPM-ALK chimeric protein in human lymphoid T-cells inhibits drug-induced, but not Fas-induced apoptosis. Oncogene 2001;20:7386–97.CrossRef
Turner, SD, Yeung, D, Hadfield, K, Cook, SJ, Alexander, DR. The NPM-ALK tyrosine kinase mimics TCR signalling pathways, inducing NFAT and AP-1 by RAS-dependent mechanisms. Cellular Signaling 2007;19:740–7.CrossRef
Matsuyama, H, Suzuki, HI, Nishimori, H, et al. miR-135b mediates NPM-ALK-driven oncogenicity and renders IL-17-producing immunophenotype to anaplastic large cell lymphoma. Blood 2011;118:6881–92.CrossRef
Voena, C, Conte, C, Ambrogio, C, et al. The tyrosine phosphatase Shp2 interacts with NPM-ALK and regulates anaplastic lymphoma cell growth and migration. Cancer Research 2007;67:4278–86.CrossRef
Ambrogio, C, Voena, C, Manazza, AD, et al. p130Cas mediates the transforming properties of the anaplastic lymphoma kinase. Blood 2005;106:3907–16.CrossRef
Piva, R, Chiarle, R, Manazza, AD, et al. Ablation of oncogenic ALK is a viable therapeutic approach for anaplastic large-cell lymphomas. Blood 2006;107:689–97.CrossRef
Ambrogio, C, Voena, C, Manazza, AD, et al. The anaplastic lymphoma kinase controls cell shape and growth of anaplastic large cell lymphoma through Cdc42 activation. Cancer Research 2008;68:8899–907.CrossRef
Colomba, A, Courilleau, D, Ramel, D, et al. Activation of Rac1 and the exchange factor Vav3 are involved in NPM-ALK signaling in anaplastic large cell lymphomas. Oncogene 2008;27:2728–36.CrossRef
Colomba, A, Giuriato, S, Dejean, E, et al. Inhibition of Rac controls NPM-ALK-dependent lymphoma development and dissemination. Blood Cancer Journal 2011;1:e21.
Sahai, E, Marshall, CJ. RHO-GTPases and cancer. Nature Reviews Cancer 2002;2:133–42.CrossRef
Billadeau, DD, Nolz, JC, Gomez, TS. Regulation of T-cell activation by the cytoskeleton. Nature Reviews Immunology 2007;7:131–43.CrossRef
Dotto, GP. Notch tumor suppressor function. Oncogene 2008;27:5115–23.CrossRef
Li, R, Xue, L, Zhu, T, et al. Design and synthesis of 5-aryl-pyridone-carboxamides as inhibitors of anaplastic lymphoma kinase. Journal of Medicinal Chemistry 2006;49:1006–15.CrossRefGoogle ScholarPubMed
Christensen, JG, Zou, HY, Arango, ME, et al. Cytoreductive antitumor activity of PF-2341066, a novel inhibitor of anaplastic lymphoma kinase and c-Met, in experimental models of anaplastic large-cell lymphoma. Molecular Cancer Therapeutics 2007;6:3314–22.CrossRef
Pulford, K, Falini, B, Banham, AH, et al. Immune response to the ALK oncogenic tyrosine kinase in patients with anaplastic large-cell lymphoma. Blood 2000;96:1605–7.
Passoni, L, Gambacorti-Passerini, C. ALK a novel lymphoma-associated tumor antigen for vaccination strategies. Leukemia and Lymphoma 2003;44:1675–81.CrossRef
Ait-Tahar, K, Cerundolo, V, Banham, AH, et al. B and CTL responses to the ALK protein in patients with ALK-positive ALCL. International Journal of Cancer 2006;118:688–95.CrossRefGoogle ScholarPubMed
Passoni, L, Gallo, B, Biganzoli, E, et al. In vivo T-cell immune response against anaplastic lymphoma kinase in patients with anaplastic large cell lymphomas. Haematologica 2006;91:48–55.
Ait-Tahar, K, Barnardo, MC, Pulford, K. CD4 T-helper responses to the anaplastic lymphoma kinase (ALK) protein in patients with ALK-positive anaplastic large-cell lymphoma. Cancer Research 2007;67:1898–901.CrossRef
Chiarle, R, Martinengo, C, Mastini, C, et al. The anaplastic lymphoma kinase is an effective oncoantigen for lymphoma vaccination. Nature Medicine 2008;14:676–80.CrossRef
Bonvini, P, Zorzi, E, Mussolin, L, et al. The effect of the cyclin-dependent kinase inhibitor flavopiridol on anaplastic large cell lymphoma cells and relationship with NPM-ALK kinase expression and activity. Haematologica 2009;94:944–55.CrossRef
Marzec, M, Kasprzycka, M, Liu, X, et al. Oncogenic tyrosine kinase NPM/ALK induces activation of the rapamycin-sensitive mTOR signaling pathway. Oncogene 2007;26:5606–14.CrossRef
Staber, PB, Vesely, P, Haq, N, et al. The oncoprotein NPM-ALK of anaplastic large-cell lymphoma induces JUNB transcription via ERK1/2 and JunB translation via mTOR signaling. Blood 2007;110:3374–83.CrossRef
Merkel, O, Hamacher, F, Sifft, E, Kenner, L, Greil, R. Novel therapeutic options in anaplastic large cell lymphoma:molecular targets and immunological tools. Molecular Cancer Therapeutics 2010;10:1127–36.CrossRef
Desjobert, C, Renalier, MH, Bergalet, J, et al. MiR-29a down-regulation in ALK-positive anaplastic large cell lymphomas contributes to apoptosis blockade through MCL-1 overexpression. Blood 2011;117:6627–37.CrossRef
Drakos, E, Atsaves, V, Schlette, E, et al. The therapeutic potential of p53 reactivation by nutlin-3a in ALK+ anaplastic large cell lymphoma with wild-type or mutated p53. Leukemia 2009;23:2290–9.CrossRef
Bonvini, P, Gastaldi, T, Falini, B, Rosolen, A. Nucleophosmin-anaplastic lymphoma kinase (NPM-ALK), a novel Hsp90-client tyrosine kinase:down-regulation of NPM-ALK expression and tyrosine phosphorylation in ALK(+) CD30(+) lymphoma cells by the Hsp90 antagonist 17-allylamino,17-demethoxygeldanamycin. Cancer Research 2002;62:1559–66.
Bonvini, P, Dalla Rosa, H, Vignes, N, Rosolen, A. Ubiquitination and proteasomal degradation of nucleophosmin-anaplastic lymphoma kinase induced by 17-allylamino-demethoxygeldanamycin:role of the co-chaperone carboxyl heat shock protein 70-interacting protein. Cancer Research 2004;64:3256–64.CrossRef
Yue, P, Turkson, J. Targeting STAT3 in cancer: how successful are we? Expert Opinion in Investigational Drugs 2009;18:45–56.
Duplantier, MM, Lamant, L, Sabourdy, F, et al. Serpin A1 is overexpressed in ALK+ anaplastic large cell lymphoma and its expression correlates with extranodal dissemination. Leukemia 2006;20:1848–54.CrossRef
Zhang, Q, Wang, HY, Liu, X, Wasik, MA. STAT5A is epigenetically silenced by the tyrosine kinase NPM1-ALK and acts as a tumor suppressor by reciprocally inhibiting NPM1-ALK expression. Nature Medicine 2007;13:1341–8.CrossRef
Tian, ZG, Longo, DL, Funakoshi, S, et al. In vivo antitumor effects of unconjugated CD30 monoclonal antibodies on human anaplastic large-cell lymphoma xenografts. Cancer Research 1995;55:5335–41.
Terenzi, A, Bolognesi, A, Pasqualucci, L, et al. Anti-CD30 (BER=H2) immunotoxins containing the type-1 ribosome-inactivating proteins momordin and PAP-S (pokeweed antiviral protein from seeds) display powerful antitumour activity against CD30+ tumour cells in vitro and in SCID mice. British Journal of Haematology 1996;92:872–9.CrossRefGoogle ScholarPubMed
Pfeifer, W, Levi, E, Petrogiannis-Haliotis, T, et al. A murine xenograft model for human CD30+ anaplastic large cell lymphoma. Successful growth inhibition with an anti-CD30 antibody (HeFi-1). American Journal of Pathology 1999;155:1353–9.CrossRefGoogle Scholar
Ansell, SM, Horwitz, SM, Engert, A, et al. Phase I/II study of an anti-CD30 monoclonal antibody (MDX-060) in Hodgkin's lymphoma and anaplastic large-cell lymphoma. Journal of Clinical Oncology 2007;25:2764–9.CrossRefGoogle ScholarPubMed
Duvic, M, Reddy, SA, Pinter-Brown, L, et al. A Phase II study of SGN-30 in cutaneous anaplastic large cell lymphoma and related lymphoproliferative disorders. Clinical Cancer Research 2009;15:6217–24.CrossRef
Forero-Torres, A, Leonard, JP, Younes, A, et al. A Phase II study of SGN-30 (anti-CD30 mAb) in Hodgkin lymphoma or systemic anaplastic large cell lymphoma. British Journal of Haematology 2009;146:171–9.CrossRefGoogle ScholarPubMed
Turner, SD, Alexander, DR. What have we learnt from mouse models of NPM-ALK-induced lymphomagenesis? Leukemia 2005;19:1128–34.
Miething, C, Peschel, C, Duyster, J. Targeting the oncogenic tyrosine kinase NPM-ALK in lymphoma:the role of murine models in defining pathogenesis and treatment options. Current Drug Targets 2006;7:1329–34.CrossRef
Kuefer, MU, Look, AT, Pulford, K, et al. Retrovirus-mediated gene transfer of NPM-ALK causes lymphoid malignancy in mice. Blood 1997;90:2901–10.
Miething, C, Grundler, R, Fend, F, et al. The oncogenic fusion protein nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) induces two distinct malignant phenotypes in a murine retroviral transplantation model. Oncogene 2003;22:4642–7.CrossRef
Lange, K, Uckert, W, Blankenstein, T, et al. Overexpression of NPM-ALK induces different types of malignant lymphomas in IL-9 transgenic mice. Oncogene 2003;22:517–27.CrossRef
Turner, SD, Tooze, R, Maclennan, K, Alexander, DR. Vav-promoter regulated oncogenic fusion protein NPM-ALK in transgenic mice causes B-cell lymphomas with hyperactive Jun kinase. Oncogene 2003;22:7750–61.CrossRef
Chiarle, R, Gong, JZ, Guasparri, I, et al. NPM-ALK transgenic mice spontaneously develop T-cell lymphomas and plasma cell tumors. Blood 2003;101:1919–27.CrossRef
Jager, R, Hahne, J, Jacob, A, et al. Mice transgenic for NPM-ALK develop non-Hodgkin lymphomas. Anticancer Research 2005;25:3191–6.
Turner, SD, Merz, H, Yeung, D, Alexander, DR. CD2 promoter regulated nucleophosmin-anaplastic lymphoma kinase in transgenic mice causes B lymphoid malignancy. Anticancer Research 2006;26:3275–9.
Delsol, G, Lamant, L, Mariame, B, et al. A new subtype of large B-cell lymphoma expressing the ALK kinase and lacking the 2;5 translocation. Blood 1997;89:1483–90.
Giuriato, S, Foisseau, M, Dejean, E, et al. Conditional TPM3-ALK and NPM-ALK transgenic mice develop reversible ALK-positive early B cell lymphoma/leukemia. Blood 2010;115:4061–70.CrossRef
Laimer, D, Dolznig, H, Kollmann, K, et al. PDGFR blockade is a rational and effective therapy for NPM-ALK-driven lymphomas. Nature Medicine 2012;18:1699–704.CrossRef
Soda, M, Takada, S, Takeuchi, K, et al. A mouse model for EML4-ALK-positive lung cancer. Proceedings of the National Academy of Sciences USA 2008;105:19 893–7.
Mduff, FK, Hook, CE, Tooze, RM, et al. Determining the contribution of NPM1 heterozygosity to NPM-ALK-induced lymphomagenesis. Laboratory Investigation 2011;91:1298–303.CrossRef
Berry, T, Luther, W, Bhatnagar, N, et al. The ALK(F1174L) mutation potentiates the oncogenic activity of MYCN in neuroblastoma. Cancer Cell 2012;22:117–30.CrossRef
Heukamp, LC, Thor, T, Schramm, A, et al. Targeted expression of mutated ALK induces neuroblastoma in transgenic mice. Science Translational Medicine 2012;4:141ra91.
Zhu, S, Lee, JS, Guo, F, et al. Activated ALK collaborates with MYCN in neuroblastoma pathogenesis. Cancer Cell 2012;21:362–73.CrossRef
Zhang, M, Yao, Z, Zhang, Z, et al. Effective therapy for a murine model of human anaplastic large-cell lymphoma with the anti-CD30 monoclonal antibody, HeFi-1, does not require activating Fc receptors. Blood 2006;108:705–10.CrossRef
Turturro, F, Heineke, HL, Drevyanko, TF, Link, CJ, Seth P. Adenovirus-p53-mediated gene therapy of anaplastic large cell lymphoma with t(2;5) in a nude mouse model. Gene Therapy 2000;7:930–3.CrossRef
Coluccia, AM, Perego, S, Cleris, L, et al. Bcl-XL down-regulation suppresses the tumorigenic potential of NPM/ALK in vitro and in vivo. Blood 2004;103:2787–94.CrossRef
Jundt, F, Raetzel, N, Muller, C, et al. A rapamycin derivative (everolimus) controls proliferation through down-regulation of truncated CCAAT enhancer binding protein (beta) and NF-(kappa)B activity in Hodgkin and anaplastic large cell lymphomas. Blood 2005;106:1801–7.CrossRef
Kruczynski, A, Mayer, P, Marchand, A, et al. Antitumor activity of pyridoisoquinoline derivatives F91873 and F91874, novel multikinase inhibitors with activity against the anaplastic lymphoma kinase. Anticancer Drugs 2009;20:364–72.CrossRef
Sabbatini, P, Korenchuk, S, Rowand, JL, et al. GSK1838705A inhibits the insulin-like growth factor-1 receptor and anaplastic lymphoma kinase and shows antitumor activity in experimental models of human cancers. Molecular Cancer Therapeutics 2009;8:2811–20.CrossRef
Wood, AC, Laudenslager, EA, Haglund, EA, et al. Inhibition of ALK mutated neuroblastomas by the selective inhibitor PF-02341066. Journal of Clinical Oncology 2009;27:10008b.Google Scholar
Lu, L, Ghose, AK, Quail, MR, et al. ALK mutants in the kinase domain exhibit altered kinase activity and differential sensitivity to small molecule ALK inhibitors. Biochemistry 2009;48:3600–9.CrossRef
Janoueix-Lerosey, I, Schleiermacher, G, Delattre, O. Molecular pathogenesis of peripheral neuroblastic tumors. Oncogene 2010;29:1566–79.CrossRef
Schulte, JH, Bachmann, HS, Brockmeyer, B, et al. High ALK receptor tyrosine kinase expression supersedes ALK mutation as a determining factor of an unfavorable phenotype in primary neuroblastoma. Clinical Cancer Research 2011;17:5082–92.CrossRef
De Brouwer, S, De Preter, K, Kumps, C, et al. Meta-analysis of neuroblastomas reveals a skewed ALK mutation spectrum in tumors with MYCN amplification. Clinical Cancer Research 2010;16:4353–62.CrossRef
Chand, D, Yamazaki, Y, Ruuth, K, et al. Cell culture and Drosophila model systems define three classes of ALK mutations in neuroblastoma. Disease Models and Mechanisms 2013;6:373–82.CrossRef
Martinsson, T, Eriksson, T, Abrahamsson, J, et al. Appearance of the novel activating F1174S ALK mutation in neuroblastoma correlates with aggressive tumor progression and unresponsiveness to therapy. Cancer Research 2011;71:98–105.CrossRef
Azarova, AM, Gautam, G, George, RE. Emerging importance of ALK in neuroblastoma. Seminars in Cancer Biology 2011;21:267–75.CrossRef
Murugan, AK, Xing, M. Anaplastic thyroid cancers harbor novel oncogenic mutations of the ALK gene. Cancer Research 2011;71:4403–11.CrossRef
Coco, S, De Mariano, M, Valdora, F, et al. Identification of ALK germline mutation (3605delG) in pediatric anaplastic medulloblastoma. Journal of Human Genetics 2012;57:682–4.CrossRefGoogle ScholarPubMed
McDuff, FK, Lim, SV, Dalbay, M, Turner, SD. Assessment of the transforming potential of novel anaplastic lymphoma kinase point mutants. Molecular Carcinogenesis 2013;52:79–83.CrossRef
Stein, H, Foss, HD, Durkop, H, et al. CD30(+) anaplastic large cell lymphoma:a review of its histopathologic, genetic, and clinical features. Blood 2000;96:3681–95.
Duyster, J, Bai, RY, Morris, SW. Translocations involving anaplastic lymphoma kinase (ALK). Oncogene 2001;20:5623–37.CrossRef
Pulford, K, Lamant, L, Espinos, E, et al. The emerging normal and disease-related roles of anaplastic lymphoma kinase. Cellular and Molecular Life Sciences 2004;61:2939–53.
Pulford, K, Morris, SW, Mason, DY. Anaplastic lymphoma kinase proteins and malignancy. Current Opinion in Hematology 2001;8:231–6.CrossRef
Delsol, G, Jaffe, ES, Falini, B, et al. Anaplastic large cell lymphoma (ALCL), ALK-positive. In: Swerdlow, SH, Campo E, Harris NL, et al., editors. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: International Agency for Research on Cancer; 2008:312–16.
Damm-Welk, C, Klapper, W, Oschlies, I, et al. Distribution of NPM1-ALK and X-ALK fusion transcripts in paediatric anaplastic large cell lymphoma:a molecular-histological correlation. British Journal of Haematology 2009;146:306–9.CrossRefGoogle ScholarPubMed
Bischof, D, Pulford, K, Mason, DY, Morris, SW. Role of the nucleophosmin (NPM) portion of the non-Hodgkin's lymphoma-associated NPM-anaplastic lymphoma kinase fusion protein in oncogenesis. Molecular and Cellular Biology 1997;17:2312–25.CrossRef
Mason, DY, Pulford, KA, Bischof, D, et al. Nucleolar localization of the nucleophosmin-anaplastic lymphoma kinase is not required for malignant transformation. Cancer Research 1998;58:1057–62.

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