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  • Print publication year: 2010
  • Online publication date: December 2010

7 - Acute lymphoblastic leukemia

from Part 2 - Hematological malignancies

Summary

Introduction

Acute lymphoblastic leukemia (ALL), also known as lymphoblastic leukemia/lymphoma in the WHO classification, is a malignant expansion of immature lymphoid cells that results from multi-step genetic changes in a single lymphoid progenitor cell. Its incidence peaks between the ages of 2 and 4 years; rates are lower during later childhood, adolescence and young adulthood but the incidence rises in the sixth decade, reaching a second, smaller peak in the elderly. ALL is the most common malignancy diagnosed in patients younger than 15 years. Childhood ALL appears to have a prenatal origin in many cases. In the case of identical twins, when leukemia occurs in one twin, there are a 20% probability that it will also occur in the other twin due to ALL transfer through the placental circulation. In identical twins with the t(4;11); (q21;q23) MLL-AFF1, the chances of ALL becoming clinically overt in the other twin in a short period of time are nearly 100%. The concordance rate in twins is lower in cases of ALL with the ETV6-RUNX1 fusion or T-cell phenotype, probably because of the requirement for additional genetic events for leukemic transformation.

A small proportion of patients (< 5%) have hereditary genetic abnormalities that predispose to the disease, including Down syndrome, ataxia telangiectasia and Bloom's syndrome; children with Down syndrome have a 10- to 30-fold higher risk of developing ALL.

References
Pui, CH, Robison, LL, Look, AT. Acute lymphoblastic leukaemia. Lancet 2008;371:1030–43.
Hong, D, Gupta, R, Ancliff, Pet al. Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia. Science 2008;319:336–9.
Trevino, LR, Yang, W, French, Det al. Germline genomic variants associated with childhood acute lymphoblastic leukemia. Nat Genet 2009;41:1001–5.
Papaemmanuil, E, Hosking, FJ, Vijayakrishnan, Jet al. Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia. Nat Genet 2009;41:1006–10.
Mullighan, CG, Goorha, S, Radtke, Iet al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 2007;446:758–64.
Familiades, J, Bousquet, M, Lafage-Pochitaloff, Met al. PAX5 mutations occur frequently in adult B-cell progenitor acute lymphoblastic leukemia and PAX5 haploinsufficiency is associated with BCR-ABL1 and TCF3-PBX1 fusion genes: a GRAALL study. Leukemia 2009;23:1989–1998.
Coustan-Smith, E, Mullighan, CG, Onciu, Met al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol 2009;10:147–56.
Rowe, JM. Optimal management of adults with ALL. Br J Haematol 2009;144:468–83.
Rubnitz, JE, Wichlan, D, Devidas, Met al. Prospective analysis of TEL gene rearrangements in childhood acute lymphoblastic leukemia: a Children's Oncology Group study. J Clin Oncol 2008;26:2186–91.
Harrison, CJ. Cytogenetics of paediatric and adolescent acute lymphoblastic leukaemia. Br J Haematol 2009;144:147–56.
Campana, D, Behm, FG. Immunophenotyping of leukemia. J Immunol Methods 2000;243:59–75.
Weerkamp, F, Dekking, E, Ng, YYet al. Flow cytometric immunobead assay for the detection of BCR-ABL fusion proteins in leukemia patients. Leukemia 2009;23:1106–17.
Vardiman, JW, Thiele, J, Arber, DAet al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009;114:937–51.
Dworzak, MN, Schumich, A, Printz, Det al. CD20 up-regulation in pediatric B-cell precursor acute lymphoblastic leukemia during induction treatment: setting the stage for anti-CD20 directed immunotherapy. Blood 2008;112:3982–8.
Mullighan, CG, Miller, CB, Radtke, Iet al. BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature 2008;453:110–14.
Ottmann, OG, Pfeifer, H. First-line treatment of Philadelphia chromosome-positive acute lymphoblastic leukaemia in adults. Curr Opin Oncol 2009;21 Suppl 1:S43–6.
Meyer, C, Kowarz, E, Hofmann, Jet al. New insights to the MLL recombinome of acute leukemias. Leukemia 2009;23:1490–9.
Pui, CH, Chessells, JM, Camitta, Bet al. Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements. Leukemia 2003;17:700–6.
Sutcliffe, MJ, Shuster, JJ, Sather, HNet al. High concordance from independent studies by the Children's Cancer Group (CCG) and Pediatric Oncology Group (POG) associating favorable prognosis with combined trisomies 4, 10, and 17 in children with NCI Standard-Risk B-precursor Acute Lymphoblastic Leukemia: a Children's Oncology Group (COG) initiative. Leukemia 2005;19:734–40.
Nachman, JB, Heerema, NA, Sather, Het al. Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia. Blood 2007;110:1112–15.
Jeha, S, Pei, D, Raimondi, SCet al. Increased risk for CNS relapse in pre-B cell leukemia with the t(1;19)/TCF3-PBX1. Leukemia 2009;23:1406–9.
Boer, ML, Slegtenhorst, M, Menezes, RXet al. A subtype of childhood acute lymphoblastic leukaemia with poor treatment outcome: a genome-wide classification study. Lancet Oncol 2009;10:125–34.
Mullighan, CG, Su, X, Zhang, Jet al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. New Engl J Med 2009;360:470–80.
Mullighan, CG, Zhang, J, Harvey, RCet al. JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci USA 2009;106:9414–18.
Ferrando, AA, Neuberg, DS, Staunton, Jet al. Gene expression signatures define novel oncogenic pathways in T cell acute lymphoblastic leukemia. Cancer Cell 2002;1:75–87.
Ferrando, AA, Neuberg, DS, Dodge, RKet al. Prognostic importance of TLX1 (HOX11) oncogene expression in adults with T-cell acute lymphoblastic leukaemia. Lancet 2004;363:535–6.
Weng, AP, Ferrando, AA, Lee, Wet al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science 2004;306:269–71.
Larson, GA, Chen, Q, Kugel, DSet al. The impact of NOTCH1, FBW7 and PTEN mutations on prognosis and downstream signaling in pediatric T-cell acute lymphoblastic leukemia: a report from the Children's Oncology Group. Leukemia 2009;23:1417–25.
Baldus, CD, Martus, P, Burmeister, Tet al. Low ERG and BAALC expression identifies a new subgroup of adult acute T-lymphoblastic leukemia with a highly favorable outcome. J Clin Oncol 2007;25:3739–45.
Campana, D. Status of minimal residual disease testing in childhood haematological malignancies. Br J Haematol 2008;143:481–9.
Gabert, J, Beillard, E, Velden, Vet al. Standardization and quality control studies of ‘real-time’ quantitative reverse transcriptase polymerase chain reaction of fusion gene transcripts for residual disease detection in leukemia – a Europe Against Cancer program. Leukemia 2003;17:2318–57.
Velden, VH, Dongen, JJ. MRD detection in acute lymphoblastic leukemia patients using Ig/TCR gene rearrangements as targets for real-time quantitative PCR. Methods Mol Biol 2009;538:115–50.
Flohr, T, Schrauder, A, Cazzaniga, Get al. Minimal residual disease-directed risk stratification using real-time quantitative PCR analysis of immunoglobulin and T-cell receptor gene rearrangements in the international multicenter trial AIEOP-BFM ALL 2000 for childhood acute lymphoblastic leukemia. Leukemia 2008;22:771–82.
Coustan-Smith, E, Sancho, J, Hancock, MLet al. Use of peripheral blood instead of bone marrow to monitor residual disease in children with acute lymphoblastic leukemia. Blood 2002;100:2399–402.
Coustan-Smith, E, Sancho, J, Hancock, MLet al. Clinical importance of minimal residual disease in childhood acute lymphoblastic leukemia. Blood 2000;96:2691–6.
Borowitz, MJ, Devidas, M, Hunger, SPet al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors. a Children's Oncology Group study. Blood 2008;111:5477–85.
Cave, H, Werff ten Bosch, J, Suciu, Set al. Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia. European Organization for Research and Treatment of Cancer – Childhood Leukemia Cooperative Group. New Engl J Med 1998;339:591–8.
Dworzak, MN, Froschl, G, Printz, Det al. Prognostic significance and modalities of flow cytometric minimal residual disease detection in childhood acute lymphoblastic leukemia. Blood 2002;99:1952–8.
Zhou, J, Goldwasser, MA, Li, Aet al. Quantitative analysis of minimal residual disease predicts relapse in children with B-lineage acute lymphoblastic leukemia in DFCI ALL Consortium Protocol 95–01. Blood 2007;110:1607–11.
Coustan-Smith, E, Sancho, J, Behm, FGet al. Prognostic importance of measuring early clearance of leukemic cells by flow cytometry in childhood acute lymphoblastic leukemia. Blood 2002;100:52–8.
Coustan-Smith, E, Ribeiro, RC, Stow, Pet al. A simplified flow cytometric assay identifies children with acute lymphoblastic leukemia who have a superior clinical outcome. Blood 2006;108:97–102.
Campana, D. Molecular determinants of treatment response in acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program 2008;366–73.
Mullighan, CG, Su, X, Zhang, Jet al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. New Engl J Med 2009;360:470–80.
Mortuza, FY, Papaioannou, M, Moreira, IMet al. Minimal residual disease tests provide an independent predictor of clinical outcome in adult acute lymphoblastic leukemia. J Clin Oncol 2002;20:1094–104.
Bruggemann, M, Raff, T, Flohr, Tet al. Clinical significance of minimal residual disease quantification in adult patients with standard-risk acute lymphoblastic leukemia. Blood 2006;107:1116–23.
Raff, T, Gokbuget, N, Luschen, Set al. Molecular relapse in adult standard-risk ALL patients detected by prospective MRD monitoring during and after maintenance treatment: data from the GMALL 06/99 and 07/03 trials. Blood 2007;109:910–15.
Bassan, R, Spinelli, O, Oldani, Eet al. Improved risk classification for risk-specific therapy based on the molecular study of MRD in adult ALL. Blood 2009;113:4153–62.
Holowiecki, J, Krawczyk-Kulis, M, Giebel, Set al. Status of minimal residual disease after induction predicts outcome in both standard and high-risk Ph-negative adult acute lymphoblastic leukaemia. The Polish Adult Leukemia Group ALL 4–2002 MRD Study. Br J Haematol 2008;142:227–37.
Wassmann, B, Pfeifer, H, Stadler, Met al. Early molecular response to posttransplantation imatinib determines outcome in MRD+ Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL). Blood 2005;106:458–63.
Pui, CH, Campana, D, Pei, Det al. Treating childhood acute lymphoblastic leukemia without cranial irradiation. New Engl J Med 2009;360:2730–41.