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6 - Cytogenetics of acute leukemias

from Section 2 - Cell biology and pathobiology

Published online by Cambridge University Press:  05 April 2013

By
Susana C. Raimondi
Edited by
Ching-Hon Pui
Ching-Hon Pui
Affiliation:
St Jude's Children's Research Hospital
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Summary

Introduction

Acute leukemia is best managed through the use of risk-adapted therapy. The karyotype of patients at diagnosis is an important factor in predicting response to therapy, and cytogenetic methods to detect the presence or absence of particular chromosomal abnormalities are key to stratifying patients by risk group. Identifying the genes involved in recurrent chromosomal abnormalities and understanding the roles of these genes in regulating cell growth and inducing malignant transformation can provide important insights into the altered biology of leukemic cells and help in devising novel risk-directed treatment strategies. This chapter reviews cytogenetic nomenclature and procedures as well as numeric and structural chromosomal abnormalities and their clinical associations, including prognosis, in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Associations between specific cytogenetic and molecular changes, and their roles in diagnosis and risk assessment are also discussed.

Conventional cytogenetics

Standard chromosomal analysis remains the method of choice for initial screening of karyotypic abnormalities in leukemic cells. Conventional cytogenetic methods detect chromosomal abnormalities in clones of mitotically active (metaphase) neoplastic cells only and are particularly efficient in identifying abnormalities associated with acute leukemias. These methods can detect an abnormal clone in 90% of children and adolescents with ALL and 80% of those with AML. They also permit the study of complex cytogenetic changes in neoplastic cells, although complementary genetic methods such as reverse transcriptase polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH) are needed to detect cryptic abnormalities or to evaluate equivocal results.

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Childhood Leukemias , pp. 135 - 167
Publisher: Cambridge University Press
Print publication year: 2012

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References

Shaffer, LG, Slovak, ML, Campbell, LJ (eds.). An International System for Human Cytogenetic Nomenclature. Cytogenetic and Genome Research 2009. Basel: Karger, 2009.Google Scholar
Pui, CH, Campana, D, Pei, D, et al. Treating childhood acute lymphoblastic leukemia without cranial irradiation. N Engl J Med 2009;360:2730–2741.CrossRefGoogle ScholarPubMed
Borowitz, MJ, Devidas, M, Hunger, SP, et 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;111:5477–5485.CrossRefGoogle ScholarPubMed
Carroll, AJ, Heerema, NA, Gastier-Foster, JM, et al. Masked hypodiploidy: hypodiploid acute lymphoblastic leukemia (ALL) in children mimicking hyperdiploid ALL: a report from the Children's Oncology Group (COG) AALL03B1 study. Blood 2009;114(Suppl 1):632a.Google Scholar
Raimondi, SC, Zhou, Y, Shurtleff, SA, et al. Near-triploidy and near-tetraploidy in childhood acute lymphoblastic leukemia: association with B-lineage blast cells carrying the ETV6–RUNX1 fusion, T-lineage immunophenotype, and favorable outcome. Cancer Genet Cytogenet 2006;169:50–57.CrossRefGoogle ScholarPubMed
Raimondi, SC, Pui, C-H, Hancock, ML, et al. Heterogeneity of hyperdiploid (51-67) childhood acute lymphoblastic leukemia. Leukemia 1996;10:213–224.Google ScholarPubMed
Sutcliffe, MJ, Shuster, JJ, Sather, HN, et 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;19:734–740.CrossRefGoogle ScholarPubMed
Raimondi, SC, Roberson, PK, Pui, CH, Behm, FG, Rivera, GK. Hyperdiploid (47-50) acute lymphoblastic leukemia in children. Blood 1992;79:3245–3252.Google ScholarPubMed
Raimondi, SC, Behm, FG, Roberson, PK, et al. Cytogenetics of childhood T-cell leukemia. Blood 1988;72:1560–1566.Google ScholarPubMed
Harrison, CJ, Moorman, AV, Broadfield, ZJ, et al. Three distinct subgroups of hypodiploidy in acute lymphoblastic leukaemia. Br J Haematol 2004;125:552–559.CrossRefGoogle ScholarPubMed
Raimondi, SC, Zhou, Y, Mathew, S, et al. Reassessment of the prognostic significance of hypodiploidy in pediatric patients with acute lymphoblastic leukemia. Cancer 2003;98:2715–2722.CrossRefGoogle ScholarPubMed
Nachman, JB, Heerema, NA, Sather, H, et al. Outcome of treatment in children with hypodiploid acute lymphoblastic leukemia. Blood 2007;110:1112–1125.CrossRefGoogle ScholarPubMed
Raimondi, SC, Behm, FG, Roberson, PK, et al. Cytogenetics of pre-B-cell acute lymphoblastic leukemia with emphasis on prognostic implications of the t(1;19). J Clin Oncol 1990;8:1380–1388.CrossRef
Wiemels, JL, Leonard, BC, Wang, Y, et al. Site-specific translocation and evidence of postnatal origin of the t(1;19) E2A-PBX1 fusion in childhood acute lymphoblastic leukemia. Proc Natl Acad Sci USA 2002;99:15101–15106.CrossRefGoogle Scholar
Privitera, E, Luciano, A, Ronchetti, D, et al. Molecular variants of the 1;19 chromosomal translocation in pediatric acute lymphoblastic leukemia (ALL). Leukemia 1994;8:554–559.PubMed
Jeha, S, Pei, D, Raimondi, SC, et al. Increased risk for CNS relapse in pre-B cell leukemia with the t(1;19)/TCF3-PBX1. Leukemia 2009;23:1406–1409.CrossRefGoogle Scholar
Prima, V, Hunger, SP. Cooperative transformation by MEF2D/DAZAP1 and DAZAP1/MEF2D fusion proteins generated by the variant t(1;19) in acute lymphoblastic leukemia. Leukemia 2007;21:2470–2475.CrossRefGoogle Scholar
Filatov, LV, Behm, FG, Pui, C-H, et al. Childhood acute lymphoblastic leukemia with equivocal chromosome markers of the t(1;19) translocation. Genes Chromosomes Cancer 1995;13:99–103.CrossRefGoogle Scholar
Inukai, T, Hirose, K, Inaba, T, et al. Hypercalcemia in childhood acute lymphoblastic leukemia: frequent implication of parathyroid hormone-related peptide and E2A-HLF from translocation 17;19. Leukemia 2007;21:288–296.CrossRefGoogle ScholarPubMed
Brambillasca, F, Mosna, G, Colombo, M, et al. Identification of a novel molecular partner of the E2A gene in childhood leukemia. Leukemia 1999;13:369–375.CrossRefGoogle ScholarPubMed
Zhong, CH, Prima, V, Liang, X, et al. E2A-ZNF384 and NOL1-E2A fusion created by a cryptic t(12;19)(p13.3;p13.3) in acute leukemia. Leukemia 2008;22:723–729.CrossRefGoogle Scholar
La, SR, Aventin, A, Crescenzi, B, et al. CIZ gene rearrangements in acute leukemia: report of a diagnostic FISH assay and clinical features of nine patients. Leukemia 2005;19:1696–1699.Google Scholar
Barber, KE, Harrison, CJ, Broadfield, ZJ, et al. Molecular cytogenetic characterization of TCF3 (E2A)/19p13.3 rearrangements in B-cell precursor acute lymphoblastic leukemia. Genes Chromosomes Cancer 2007;46:478–486.CrossRefGoogle ScholarPubMed
Schultz, KR, Bowman, WP, Aledo, A, et al. Improved early event-free survival with imatinib in Philadelphia chromosome-positive acute lymphoblastic leukemia: a Children's Oncology Group study. J Clin Oncol 2009;27:5175–5181.CrossRefGoogle ScholarPubMed
Heerema, NA, Harbott, J, Galimberti, S, et al. Secondary cytogenetic aberrations in childhood Philadelphia chromosome positive acute lymphoblastic leukemia are nonrandom and may be associated with outcome. Leukemia 2004;18:693–702.CrossRefGoogle ScholarPubMed
Morris, CM, Kennedy, M, Heisterkamp, N, et al. A complex chromosome rearrangement forms the BCR-ABL fusion gene in leukemic cells with a normal karyotype. Genes Chromosomes Cancer 1991;3:263–271.CrossRefGoogle ScholarPubMed
Huntly, BJ, Reid, AG, Bench, AJ, et al. Deletions of the derivative chromosome 9 occur at the time of the Philadelphia translocation and provide a powerful and independent prognostic indicator in chronic myeloid leukemia. Blood 2001;98:1732–1738.CrossRefGoogle ScholarPubMed
Robinson, HM, Martineau, M, Harris, RL, et al. Derivative chromosome 9 deletions are a significant feature of childhood Philadelphia chromosome positive acute lymphoblastic leukaemia. Leukemia 2005;19:564–571.CrossRefGoogle ScholarPubMed
Mullighan, CG, Miller, CB, Radtke, I, et al. BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of IKAROS. Nature 2008;453:110–114.CrossRefGoogle ScholarPubMed
Mullighan, CG, Su, X, Zhang, J, et al. Deletion of IKZF1 and prognosis in acute lymphoblastic leukemia. N Engl J Med 2009;360:470–480.CrossRefGoogle ScholarPubMed
Martinelli, G, Iacobucci, I, Storlazzi, CT, et al. IKZF1 (Ikaros) deletions in BCR-ABL1-positive acute lymphoblastic leukemia are associated with short disease-free survival and high rate of cumulative incidence of relapse: a GIMEMA AL WP report. J Clin Oncol 2009;27:5202–5207.CrossRefGoogle ScholarPubMed
Mullighan, CG, Goorha, S, Radtke, I, et al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 2007;446:758–764.CrossRefGoogle ScholarPubMed
An, Q, Wright, SL, Konn, ZJ, et al. Variable breakpoints target PAX5 in patients with dicentric chromosomes: a model for the basis of unbalanced translocations in cancer. Proc Natl Acad Sci USA 2008;105:17050–17054.CrossRefGoogle Scholar
Lonnerholm, G, Nordgren, A, Frost, BM, et al. Dic(9;20)(p13;q11) in childhood acute lymphoblastic leukaemia is related to low cellular resistance to asparaginase, cytarabine and corticosteroids. Leukemia 2009;23:209–212.CrossRefGoogle ScholarPubMed
An, Q, Wright, SL, Moorman, AV, et al. Heterogeneous breakpoints in patients with acute lymphoblastic leukemia and the dic(9;20)(p11–13;q11) show recurrent involvement of genes at 20q11.21. Haematologica 2009;94:1164–1169.CrossRefGoogle ScholarPubMed
Familiades, J, Bousquet, M, Lafage-Pochitaloff, M, et 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.CrossRefGoogle ScholarPubMed
Nebral, K, Denk, D, Attarbaschi, A, et al. Incidence and diversity of PAX5 fusion genes in childhood acute lymphoblastic leukemia. Leukemia 2009;23:134–143.CrossRefGoogle ScholarPubMed
Krieger, D, Moericke, A, Oschlies, I, et al. Frequency and clinical relevance of DNA microsatellite alterations of the CDKN2A/B, ATM and p53 gene loci: a comparison between pediatric precursor T-cell lymphoblastic lymphoma and T-cell lymphoblastic leukemia. Haematologica 2010;95:158–162.CrossRefGoogle ScholarPubMed
Sulong, S, Moorman, AV, Irving, JA, et al. A comprehensive analysis of the CDKN2A gene in childhood acute lymphoblastic leukemia reveals genomic deletion, copy number neutral loss of heterozygosity, and association with specific cytogenetic subgroups. Blood 2009;113:100–107.CrossRefGoogle ScholarPubMed
Ramakers-van Woerden, NL, Pieters, R, Slater, RM, et al. In vitro drug resistance and prognostic impact of p16INK4A/p15INK4B deletions in childhood T-cell acute lymphoblastic leukaemia. Br J Haematol 2001;112:680–690.CrossRefGoogle ScholarPubMed
Arico, M, Ziino, O, Valsecchi, MG, et al. Acute lymphoblastic leukemia and Down syndrome: presenting features and treatment outcome in the experience of the Italian Association of Pediatric Hematology and Oncology (AIEOP). Cancer 2008;113:515–521.CrossRefGoogle Scholar
Bercovich, D, Ganmore, I, Scott, LM, et al. Mutations of JAK2 in acute lymphoblastic leukaemias associated with Down's syndrome. Lancet 2008;372:1484–1492.CrossRefGoogle ScholarPubMed
Kearney, L, de Gonzalez, CD, Yeung, J, et al. Specific JAK2 mutation (JAK2R683) and multiple gene deletions in Down syndrome acute lymphoblastic leukemia. Blood 2009;113:646–648.CrossRefGoogle ScholarPubMed
Mullighan, CG, Zhang, J, Harvey, RC, et al. JAK mutations in high-risk childhood acute lymphoblastic leukemia. Proc Natl Acad Sci USA 2009;106:9414–9418.CrossRefGoogle ScholarPubMed
Yoda, A, Yoda, Y, Chiaretti, S, et al. Functional screening identifies CRLF2 in precursor B-cell acute lymphoblastic leukemia. Proc Natl Acad Sci USA 2010;107:252–257.CrossRefGoogle ScholarPubMed
Hertzberg, L, Vendramini, E, Ganmore, I, et al. Down syndrome acute lymphoblastic leukemia, a highly heterogeneous disease in which aberrant expression of CRLF2 is associated with mutated JAK2: a report from the International BFM Study Group. Blood 2010;115:1006–1017.CrossRefGoogle ScholarPubMed
Russell, LJ, Capasso, M, Vater, I, et al. Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. Blood 2009;114:2688–2698.CrossRefGoogle ScholarPubMed
Mullighan, CG, Collins-Underwood, JR, Phillips, LA, et al. Rearrangement of CRLF2 in B-progenitor- and Down syndrome-associated acute lymphoblastic leukemia. Nat Genet 2009;41:1243–1246.CrossRefGoogle ScholarPubMed
Pieters, R, Schrappe, M, de Laat, P, et al. A treatment protocol for infants younger than 1 year with acute lymphoblastic leukaemia (Interfant-99): an observational study and a multicentre randomised trial. Lancet 2007;370:240–250.CrossRefGoogle Scholar
Pui, CH, Gaynon, PS, Boyett, JM, et al. Outcome of treatment in childhood acute lymphoblastic leukaemia with rearrangements of the 11q23 chromosomal region. Lancet 2002;359:1909–1915.CrossRefGoogle ScholarPubMed
Raimondi, SC, Frestedt, JL, Pui, CH, et al. Acute lymphoblastic leukemias with deletion of 11q23 or a novel inversion (11)(p13q23) lack MLL gene rearrangements and have favorable clinical features. Blood 1995;86:1881–1886.Google ScholarPubMed
Meyer, C, Kowarz, E, Hofmann, J, et al. New insights to the MLL recombinome of acute leukemias. Leukemia 2009;23:1490–1499.CrossRefGoogle ScholarPubMed
Hilden, JM, Dinndorf, PA, Meerbaum, SO, et al. Analysis of prognostic factors of acute lymphoblastic leukemia in infants: report on CCG 1953 from the Children's Oncology Group. Blood 2006; 108:441–451.
Tomizawa, D, Koh, K, Hirayama, M, et al. Outcome of recurrent or refractory acute lymphoblastic leukemia in infants with MLL gene rearrangements: a report from the Japan Infant Leukemia Study Group. Pediatr Blood Cancer 2009;52:808–813.CrossRefGoogle ScholarPubMed
Armstrong, SA, Staunton, JE, Silverman, LB, et al. MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia. Nat Genet 2002;30:41–47.CrossRefGoogle ScholarPubMed
Stam, RW, den Boer, ML, Schneider, P, et al. Targeting FLT3 in primary MLL-gene-rearranged infant acute lymphoblastic leukemia. Blood 2005;106:2484–2490.CrossRefGoogle ScholarPubMed
Raimondi, SC, Shurtleff, SA, Downing, JR, et al. 12p abnormalities and the TEL gene (ETV6) in childhood acute lymphoblastic leukemia. Blood 1997;90:4559–4566.Google Scholar
United Kingdom Cancer Cytogenetics Group. Translocation involving 9p and/or 12p in acute lymphoblastic leukemia. Genes Chromosomes Cancer 1992;5:255–259.CrossRefGoogle Scholar
Bohlander, SK. ETV6: a versatile player in leukemogenesis. Semin Cancer Biol 2005;15:162–174.CrossRefGoogle ScholarPubMed
Romana, SP, Poirel, H, Le Coniat, M, et al. High frequency of t(12;21) in childhood B-lineage acute lymphoblastic leukemia. Blood 1995;86:4263–4269.Google Scholar
Shurtleff, SA, Buijs, A, Behm, FG, et al. TEL/AML1 fusion resulting from a cryptic t(12;21) is the most common genetic lesion in pediatric ALL and defines a subgroup of patients with an excellent prognosis. Leukemia 1995;9:1985–1989.Google Scholar
Rubnitz, JE, Wichlan, D, Devidas, M, et al. Prospective analysis of TEL gene rearrangements in childhood acute lymphoblastic leukemia: a Children's Oncology Group study. J Clin Oncol 2008;26:2186–2191.CrossRefGoogle ScholarPubMed
Forestier, E, Heyman, M, Andersen, MK, et al. Outcome of ETV6/RUNX1-positive childhood acute lymphoblastic leukaemia in the NOPHO-ALL-1992 protocol: frequent late relapses but good overall survival. Br J Haematol 2008;140:665–672.CrossRefGoogle ScholarPubMed
Zuna, J, Ford, AM, Peham, M, et al. TEL deletion analysis supports a novel view of relapse in childhood acute lymphoblastic leukemia. Clin Cancer Res 2004;10:5355–5360.CrossRefGoogle ScholarPubMed
Mullighan, CG, Phillips, LA, Su, X, et al. Genomic analysis of the clonal origins of relapsed acute lymphoblastic leukemia. Science 2008;322:1377–1380.CrossRefGoogle ScholarPubMed
Wiemels, JL, Hofmann, J, Kang, M, et al. Chromosome 12p deletions in TEL-AML1 childhood acute lymphoblastic leukemia are associated with retrotransposon elements and occur postnatally. Cancer Res 2008;68:9935–9944.CrossRefGoogle ScholarPubMed
Mathew, S, Shurtleff, SA, Raimondi, SC. Novel cryptic, complex rearrangements involving ETV6-CBFA2 (TEL-AML1) genes identified by fluorescence in situ hybridization in pediatric patients with acute lymphoblastic leukemia. Genes Chromosomes Cancer 2001;32: 188–193.CrossRefGoogle ScholarPubMed
Jalali, GR, An, Q, Konn, ZJ, et al. Disruption of ETV6 in intron 2 results in upregulatory and insertional events in childhood acute lymphoblastic leukaemia. Leukemia 2008;22:114–123.CrossRefGoogle ScholarPubMed
Graux, C, Stevens-Kroef, M, Lafage, M, et al. Heterogeneous patterns of amplification of the NUP214-ABL1 fusion gene in T-cell acute lymphoblastic leukemia. Leukemia 2009;23:125–133.CrossRefGoogle ScholarPubMed
Strefford, JC, van Delft, FW, Robinson, HM, et al. Complex genomic alterations and gene expression in acute lymphoblastic leukemia with intrachromosomal amplification of chromosome 21. Proc Natl Acad Sci USA 2006;103:8167–8172.CrossRefGoogle ScholarPubMed
Moorman, AV, Richards, SM, Robinson, HM, et al. Prognosis of children with acute lymphoblastic leukemia (ALL) and intrachromosomal amplification of chromosome 21 (iAMP21). Blood 2007;109:2327–2330.CrossRef
Attarbaschi, A, Mann, G, Panzer-Grumayer, R, et al. Minimal residual disease values discriminate between low and high relapse risk in children with B-cell precursor acute lymphoblastic leukemia and an intrachromosomal amplification of chromosome 21: the Austrian and German acute lymphoblastic leukemia Berlin–Frankfurt–Münster (ALL-BFM) trials. J Clin Oncol 2008;26:3046–3050.CrossRefGoogle ScholarPubMed
Heerema, NA, Raetz, EA, Carroll, AJ, et al. iAML1 is associated with inferior outcomes in children with acute lymphoblastic leukemia (ALL). Children's Oncology Group (COG) on contemporary studies. Blood 2011;118(Suppl 1):739a.
Patte, C, Auperin, A, Michon, J, et al. The Societe Francaise d'Oncologie Pediatrique LMB89 protocol: highly effective multiagent chemotherapy tailored to the tumor burden and initial response in 561 unselected children with B-cell lymphomas and L3 leukemia. Blood 2001;97:3370–3379.CrossRefGoogle ScholarPubMed
Navid, F, Mosijczuk, AD, Head, DR, et al. Acute lymphoblastic leukemia with the (8;14)(q24;q32) translocation and FAB L3 morphology associated with a B-precursor immunophenotype: the Pediatric Oncology Group experience. Leukemia 1999;13:135–141.CrossRefGoogle ScholarPubMed
Poppe, B, De, PP, Michaux, L, et al. PAX5/IGH rearrangement is a recurrent finding in a subset of aggressive B-NHL with complex chromosomal rearrangements. Genes Chromosomes Cancer 2005;44: 218–223.CrossRefGoogle Scholar
Russell, LJ, Akasaka, T, Majid, A, et al. t(6;14)(p22;q32): a new recurrent IGH@ translocation involving ID4 in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Blood 2008;111:387–391.CrossRef
Russell, LJ, de Castro, DG, Griffiths, M, et al. A novel translocation, t(14;19)(q32;p13), involving IGH@ and the cytokine receptor for erythropoietin. Leukemia 2009;23:614–617.CrossRefGoogle Scholar
Akasaka, T, Balasas, T, Russell, LJ, et al. Five members of the CEBP transcription factor family are targeted by recurrent IGH translocations in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Blood 2007;109:3451–3461.CrossRef
Goldberg, JM, Silverman, LB, Levy, DE, et al. Childhood T-cell acute lymphoblastic leukemia: the Dana-Farber Cancer Institute acute lymphoblastic leukemia consortium experience. J Clin Oncol 2003;21:3616–3622.CrossRefGoogle ScholarPubMed
Coustan-Smith, E, Mullighan, CG, Onciu, M, et al. Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemia. Lancet Oncol 2009;10:147–156.CrossRefGoogle ScholarPubMed
Van Vlierberghe, P, Pieters, R, Beverloo, HB, Meijerink, JP. Molecular-genetic insights in paediatric T-cell acute lymphoblastic leukaemia. Br J Haematol 2008;143:153–168.CrossRefGoogle ScholarPubMed
van Grotel, M, Meijerink, JP, van Wering, ER, et al. Prognostic significance of molecular-cytogenetic abnormalities in pediatric T-ALL is not explained by immunophenotypic differences. Leukemia 2008;22:124–131.CrossRefGoogle Scholar
Van Vlierberghe, P, Homminga, I, Zuurbier, L, et al. Cooperative genetic defects in TLX3 rearranged pediatric T-ALL. Leukemia 2008;22:762–770.CrossRefGoogle ScholarPubMed
Ballerini, P, Landman-Parker, J, Cayuela, JM, et al. Impact of genotype on survival of children with T-cell acute lymphoblastic leukemia treated according to the French protocol FRALLE-93: the effect of TLX3/HOX11L2 gene expression on outcome. Haematologica 2008;93:1658–1665.CrossRefGoogle Scholar
Attarbaschi, A, Pisecker, M, Inthal, A, et al. Prognostic relevance of TLX3 (HOX11L2) expression in childhood T-cell acute lymphoblastic leukaemia treated with Berlin–Frankfurt–Münster (BFM) protocols containing early and late re-intensification elements. Br J Haematol 2009;148:293–300.CrossRefGoogle ScholarPubMed
Clappier, E, Cuccuini, W, Kalota, A, et al. The C-MYB locus is involved in chromosomal translocation and genomic duplications in human T-cell acute leukemia (T-ALL), the translocation defining a new T-ALL subtype in very young children. Blood 2007;110:1251–1261.CrossRefGoogle Scholar
Lahortiga, I, de Keersmaecker, K, Van Vlierberghe, P, et al. Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia. Nat Genet 2007;39:593–595.CrossRefGoogle ScholarPubMed
Gorello, P, La, SR, Varasano, E, et al. Combined interphase fluorescence in situ hybridization elucidates the genetic heterogeneity of T-cell acute lymphoblastic leukemia in adults. Haematologica 2010;95:79–86.CrossRefGoogle ScholarPubMed
Cauwelier, B, Cave, H, Gervais, C, et al. Clinical, cytogenetic and molecular characteristics of 14 T-ALL patients carrying the TCRbeta-HOXA rearrangement: a study of the Groupe Francophone de Cytogenetique Hematologique. Leukemia 2007;21:121–128.CrossRefGoogle ScholarPubMed
Clappier, E, Cuccuini, W, Cayuela, JM, et al. Cyclin D2 dysregulation by chromosomal translocations to TCR loci in T-cell acute lymphoblastic leukemias. Leukemia 2006;20:82–86.CrossRefGoogle ScholarPubMed
Karrman, K, Kjeldsen, E, Lassen, C, et al. The t(X;7)(q22;q34) in paediatric T-cell acute lymphoblastic leukaemia results in overexpression of the insulin receptor substrate 4 gene through illegitimate recombination with the T-cell receptor beta locus. Br J Haematol 2009;144:546–551.CrossRefGoogle Scholar
de Keersmaecker, K, Graux, C, Odero, MD, et al. Fusion of EML1 to ABL1 in T-cell acute lymphoblastic leukemia with cryptic t(9;14)(q34;q32). Blood 2005;105:4849–4852.CrossRefGoogle Scholar
Deenik, W, Beverloo, HB, van der Poel-van de Luytgaarde, SC, et al. Rapid complete cytogenetic remission after upfront dasatinib monotherapy in a patient with a NUP214-ABL1-positive T-cell acute lymphoblastic leukemia. Leukemia 2009;23:627–629.CrossRefGoogle Scholar
Quintas-Cardama, A, Tong, W, Manshouri, T, et al. Activity of tyrosine kinase inhibitors against human NUP214-ABL1-positive T cell malignancies. Leukemia 2008;22:1117–1124.CrossRefGoogle ScholarPubMed
Suzuki, S, Nagel, S, Schneider, B, et al. A second NOTCH1 chromosome rearrangement: t(9;14)(q34.3;q11.2) in T-cell neoplasia. Leukemia 2009;23:1003–1006.CrossRefGoogle Scholar
Zhu, YM, Zhao, WL, Fu, JF, et al. NOTCH1 mutations in T-cell acute lymphoblastic leukemia: prognostic significance and implication in multifactorial leukemogenesis. Clin Cancer Res 2006;12:3043–3049.CrossRefGoogle ScholarPubMed
Van Vlierberghe, P, Meijerink, JP, Lee, C, et al. A new recurrent 9q34 duplication in pediatric T-cell acute lymphoblastic leukemia. Leukemia 2006;20:1245–1253.CrossRefGoogle ScholarPubMed
Breit, S, Stanulla, M, Flohr, T, et al. Activating NOTCH1 mutations predict favorable early treatment response and long-term outcome in childhood precursor T-cell lymphoblastic leukemia. Blood 2006;108:1151–1157.CrossRefGoogle ScholarPubMed
Asnafi, V, Buzyn, A, Le, NS, et al. NOTCH1/FBXW7 mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study. Blood 2009;113:3918–3924.CrossRefGoogle Scholar
Eguchi-Ishimae, M, Eguchi, M, Kempski, H, Greaves, M. NOTCH1 mutation can be an early, prenatal genetic event in T-ALL. Blood 2008;111:376–378.CrossRefGoogle ScholarPubMed
Flex, E, Petrangeli, V, Stella, L, et al. Somatically acquired JAK1 mutations in adult acute lymphoblastic leukemia. J Exp Med 2008;205:751–758.CrossRefGoogle ScholarPubMed
Van Vlierberghe, P, van Grotel, M, Beverloo, HB, et al. The cryptic chromosomal deletion del(11)(p12p13) as a new activation mechanism of LMO2 in pediatric T-cell acute lymphoblastic leukemia. Blood 2006;108:3520–3529.CrossRefGoogle ScholarPubMed
Bergeron, J, Clappier, E, Radford, I, et al. Prognostic and oncogenic relevance of TLX1/HOX11 expression level in T-ALLs. Blood 2007;110:2324–2330.CrossRefGoogle ScholarPubMed
Swerdlow, SH, Campos, E, Harris, NL, et al. (eds.). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Lyon: IARC Press, 2008.Google Scholar
Vardiman, JW, Thiele, J, Arber, DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009;114:937–951.CrossRefGoogle ScholarPubMed
Tsukimoto, I, Tawa, A, Horibe, K, et al. Risk-stratified therapy and the intensive use of cytarabine improves the outcome in childhood acute myeloid leukemia: The AML99 trial from the Japanese childhood AML cooperative study group. J Clin Oncol 2009;27:4007–4013.CrossRefGoogle ScholarPubMed
Rubnitz, JE, Crews, KR, Pounds, S, et al. Combination of cladribine and cytarabine is effective for childhood acute myeloid leukemia: results of the St. Jude AML97 trial. Leukemia 2009;23:1410–1416.CrossRefGoogle ScholarPubMed
Razzouk, BI, Estey, E, Pounds, S, et al. Impact of age on outcome of pediatric acute myeloid leukemia: a report from 2 institutions. Cancer 2006;106:2495–2502.CrossRefGoogle ScholarPubMed
Lange, BJ, Smith, FO, Feusner, J, et al. Outcomes in CCG-2961, a Children's Oncology Group phase 3 trial for untreated pediatric acute myeloid leukemia: a report from the Children's Oncology Group. Blood 2008;111:1044–1053.CrossRefGoogle ScholarPubMed
Mrozek, K, Marcucci, G, Paschka, P, Whitman, SP, Bloomfield, CD. Clinical relevance of mutations and gene-expression changes in adult acute myeloid leukemia with normal cytogenetics: are we ready for a prognostically prioritized molecular classification?Blood 2007;109:431–448.CrossRefGoogle ScholarPubMed
Falini, B, Sportoletti, P, Martelli, MP. Acute myeloid leukemia with mutated NPM1: diagnosis, prognosis and therapeutic perspectives. Curr Opin Oncol 2009;21:573–581.CrossRefGoogle ScholarPubMed
Brown, P, McIntyre, E, Rau, R, et al. The incidence and clinical significance of nucleophosmin mutations in childhood AML. Blood 2007;110:979–985.CrossRefGoogle ScholarPubMed
Haferlach, C, Mecucci, C, Schnittger, S, et al. AML with mutated NPM1 carrying a normal or aberrant karyotype show overlapping biologic, pathologic, immunophenotypic, and prognostic features. Blood 2009;114:3024–3032.CrossRefGoogle Scholar
Ho, PA, Alonzo, TA, Gerbing, RB, et al. Prevalence and prognostic implications of CEBPA mutations in pediatric acute myeloid leukemia (AML): a report from the Children's Oncology Group. Blood 2009;113:6558–6566.CrossRefGoogle ScholarPubMed
Raimondi, SC, Chang, MN, Ravindranath, Y, et al. Chromosomal abnormalities in 478 children with acute myeloid leukemia: clinical characteristics and treatment outcome in a cooperative pediatric oncology group study-POG 8821. Blood 1999;94:3707–3716.Google Scholar
Grimwade, D, Walker, H, Oliver, F, et al. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1612 patients entered into the MRC AML 10 trial. The Medical Research Council Adult and Children's Leukaemia Working Parties. Blood 1998;92:2322–2333.Google ScholarPubMed
Ebert, BL, Pretz, J, Bosco, J, et al. Identification of RPS14 as a 5q-syndrome gene by RNA interference screen. Nature 2008;451:335–339.CrossRefGoogle ScholarPubMed
Luna-Fienman, S, Shannon, KM, Lange, B. Childhood monosomy 7: epidemiology, biology, and mechanistic implications. Blood 1995;85:1985–1999.Google Scholar
Hasle, H, Alonzo, TA, Auvrignon, A, et al. Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study. Blood 2007;109:4641–4647.CrossRefGoogle Scholar
Schaich, M, Schlenk, RF, Al-Ali, HK, et al. Prognosis of acute myeloid leukemia patients up to 60 years of age exhibiting trisomy 8 within a non-complex karyotype: individual patient data-based meta-analysis of the German Acute Myeloid Leukemia Intergroup. Haematologica 2007;92:763–770.CrossRefGoogle ScholarPubMed
Basecke, J, Whelan, JT, Griesinger, F, Bertrand, FE. The MLL partial tandem duplication in acute myeloid leukaemia. Br J Haematol 2006;135:438–449.CrossRefGoogle ScholarPubMed
Shimada, A, Taki, T, Tabuchi, K, et al. Tandem duplications of MLL and FLT3 are correlated with poor prognoses in pediatric acute myeloid leukemia: a study of the Japanese childhood AML Cooperative Study Group. Pediatr Blood Cancer 2008;50:264–269.CrossRefGoogle ScholarPubMed
Rege-Cambrin, G, Giugliano, E, Michaux, L, et al. Trisomy 11 in myeloid malignancies is associated with internal tandem duplication of both MLL and FLT3 genes. Haematologica 2005;90:262–264.Google ScholarPubMed
McGrattan, P, Alexander, HD, Humphreys, MW, Kettle, PJ. Tetrasomy 13 as the sole cytogenetic abnormality in acute myeloid leukemia M1 without maturation. Cancer Genet Cytogenet 2002;135:192–195.CrossRefGoogle Scholar
Fehniger, TA, Byrd, JC, Marcucci, G, et al. Single-agent lenalidomide induces complete remission of acute myeloid leukemia in patients with isolated trisomy 13. Blood 2009;113:1002–1005.CrossRefGoogle ScholarPubMed
Dicker, F, Haferlach, C, Kern, W, Haferlach, T, Schnittger, S. Trisomy 13 is strongly associated with AML1/RUNX1 mutations and increased FLT3 expression in acute myeloid leukemia. Blood 2007;110:1308–1316.CrossRefGoogle ScholarPubMed
Xavier, AC, Ge, Y, Taub, JW. Down syndrome and malignancies: a unique clinical relationship: a paper from the 2008 William Beaumont hospital symposium on molecular pathology. J Mol Diagn 2009;11:371–380.CrossRefGoogle Scholar
Gamis, AS, Woods, WG, Alonzo, TA, et al. Increased age at diagnosis has a significantly negative effect on outcome in children with Down syndrome and acute myeloid leukemia: a report from the Children's Cancer Group Study 2891. J Clin Oncol 2003;21:3415–3422.CrossRefGoogle Scholar
Forestier, E, Izraeli, S, Beverloo, B, et al. Cytogenetic features of acute lymphoblastic and myeloid leukemias in pediatric patients with Down syndrome: an iBFM-SG study. Blood 2008;111:1575–1583.CrossRefGoogle ScholarPubMed
Klusmann, JH, Creutzig, U, Zimmermann, M, et al. Treatment and prognostic impact of transient leukemia in neonates with Down syndrome. Blood 2008;111:2991–2998.CrossRefGoogle ScholarPubMed
Preudhomme, C, Warot-Loze, D, Roumier, C, et al. High incidence of biallelic point mutations in the Runt domain of the AML1/PEBP2alpha B gene in M0 acute myeloid leukemia and in myeloid malignancies with acquired trisomy 21. Blood 2000;96:2862–2869.Google Scholar
Ripperger, T, Steinemann, D, Gohring, G, et al. A novel pedigree with heterozygous germline RUNX1 mutation causing familial MDS-related AML: can these families serve as a multistep model for leukemic transformation?Leukemia 2009;23:1364–1366.CrossRefGoogle ScholarPubMed
Owen, CJ, Toze, CL, Koochin, A, et al. Five new pedigrees with inherited RUNX1 mutations causing familial platelet disorder with propensity to myeloid malignancy. Blood 2008;112:4639–4645.CrossRefGoogle ScholarPubMed
Preudhomme, C, Renneville, A, Bourdon, V, et al. High frequency of RUNX1 biallelic alteration in acute myeloid leukemia secondary to familial platelet disorder. Blood 2009;113:5583–5587.CrossRefGoogle ScholarPubMed
Shinawi, M, Erez, A, Shardy, DL, et al. Syndromic thrombocytopenia and predisposition to acute myelogenous leukemia caused by constitutional microdeletions on chromosome 21q. Blood 2008;112:1042–1047.CrossRefGoogle ScholarPubMed
Wechsler, J, Greene, M, McDevitt, MA, et al. Acquired mutations in GATA1 in the megakaryoblastic leukemia of Down syndrome. Nat Genet 2002;32:148–152.CrossRefGoogle Scholar
Cabelof, DC, Patel, HV, Chen, Q, et al. Mutational spectrum at GATA1 provides insights into mutagenesis and leukemogenesis in Down syndrome. Blood 2009;114:2753–2763.CrossRefGoogle ScholarPubMed
Malinge, S, Izraeli, S, Crispino, JD. Insights into the manifestations, outcomes, and mechanisms of leukemogenesis in Down syndrome. Blood 2009;113:2619–2628.CrossRefGoogle ScholarPubMed
Roy, A, Roberts, I, Norton, A, Vyas, P. Acute megakaryoblastic leukaemia (AMKL) and transient myeloproliferative disorder (TMD) in Down syndrome: a multi-step model of myeloid leukaemogenesis. Br J Haematol 2009;147:3–12.CrossRefGoogle ScholarPubMed
Frankfurt, O, Licht, JD, Tallman, MS. Molecular characterization of acute myeloid leukemia and its impact on treatment. Curr Opin Oncol 2007;19:635–649.CrossRefGoogle ScholarPubMed
Dohner, K, Dohner, H. Molecular characterization of acute myeloid leukemia. Haematologica 2008;93:976–982.CrossRefGoogle ScholarPubMed
Byrd, JC, Ruppert, AS, Mrozek, K, et al. Repetitive cycles of high-dose cytarabine benefit patients with acute myeloid leukemia and inv(16)(p13q22) or t(16;16)(p13;q22): results from CALGB 8461. J Clin Oncol 2004;22:1087–1094.CrossRefGoogle ScholarPubMed
Gamerdinger, U, Teigler-Schlegel, A, Pils, S, et al. Cryptic chromosomal aberrations leading to an AML1/ETO rearrangement are frequently caused by small insertions. Genes Chromosomes Cancer 2003;36:261–272.CrossRefGoogle Scholar
Godon, C, Proffitt, J, Dastugue, N, et al. Large deletions 5′ to the ETO breakpoint are recurrent events in patients with t(8;21) acute myeloid leukemia. Leukemia 2002;16:1752–1754.CrossRefGoogle Scholar
Specchia, G, Albano, F, Anelli, L, et al. Insertions generating the 5′RUNX1/3′CBFA2T1 gene in acute myeloid leukemia cases show variable breakpoints. Genes Chromosomes Cancer 2004;41:86–91.CrossRefGoogle ScholarPubMed
Kuchenbauer, F, Schnittger, S, Look, T, et al. Identification of additional cytogenetic and molecular genetic abnormalities in acute myeloid leukaemia with t(8;21)/AML1- ETO. Br J Haematol 2006;134: 616–619.CrossRefGoogle Scholar
Udayakumar, AM, Alkindi, S, Pathare, AV, Raeburn, JA. Complex t(8;13;21)(q22;q14;q22) -a novel variant of t(8;21) in a patient with acute myeloid leukemia (AML-M2). Arch Med Res 2008;39:252–256.CrossRef
Ahmad, F, Kokate, P, Chheda, P, et al. Molecular cytogenetic findings in a three-way novel variant of t(1;8;21)(p35;q22;q22): a unique relocation of the AML1/ETO fusion gene 1p35 in AML-M2. Cancer Genet Cytogenet 2008;180:153–157.CrossRefGoogle Scholar
Basecke, J, Cepek, L, Mannhalter, C, et al. Transcription of AML1/ETO in bone marrow and cord blood of individuals without acute myelogenous leukemia. Blood 2002;100:2267–2268.CrossRefGoogle ScholarPubMed
Wiemels, JL, Xiao, Z, Buffler, PA, et al. In utero origin of t(8;21) AML1-ETO translocations in childhood acute myeloid leukemia. Blood 2002;99:3801–3805.CrossRefGoogle Scholar
Razzouk, BI, Raimondi, SC, Srivastava, DK, et al. Impact of treatment on the outcome of acute myeloid leukemia with inversion 16: a single institution's experience. Leukemia 2001;15:1326–1330.CrossRefGoogle ScholarPubMed
Macedo Silva, ML, Raimondi, SC, et al. Banding and molecular cytogenetic studies detected a CBFB-MYH11 fusion gene that appeared as abnormal chromosomes 1 and 16 in a baby with acute myeloid leukemia FAB M4-Eo. Cancer Genet Cytogenet 2008;182:56–60.CrossRefGoogle Scholar
Ohsaka, A, Otsubo, K, Yokota, H, et al. Spectral karyotyping and fluorescence in situ hybridization analyses identified a novel three-way translocation involving inversion 16 in therapy-related acute myeloid leukemia M4eo. Cancer Genet Cytogenet 2008;184:113–118.CrossRefGoogle ScholarPubMed
Mrozek, K, Marcucci, G, Paschka, P, Bloomfield, CD. Advances in molecular genetics and treatment of core-binding factor acute myeloid leukemia. Curr Opin Oncol 2008;20:711–718.CrossRefGoogle ScholarPubMed
Downing, JR. The AML1–ETO chimaeric transcription factor in acute myeloid leukaemia: biology and clinical significance. Br J Haematol 1999;106:296–308.CrossRefGoogle ScholarPubMed
Lutterbach, B, Hiebert, SW. Role of the transcription factor AML-1 in acute leukemia and hematopoietic differentiation. Gene 2000;245:223–235.CrossRefGoogle ScholarPubMed
Kolomietz, E, Al Maghrabi, J, Brennan, S, et al. Primary chromosomal rearrangements of leukemia are frequently accompanied by extensive submicroscopic deletions and may lead to altered prognosis. Blood 2001;97:3581–3588.CrossRefGoogle ScholarPubMed
Batanian, JR, Huang, Y, Fallon, R. Deletion of 3′-CBFB gene in association with an inversion (16)(p13q22) and a loss of the Y chromosome in a 2-year-old child with acute myelogenous leukemia-M4. Cancer Genet Cytogenet 2000;121:216–219.CrossRefGoogle Scholar
Aventin, A, La Starza, R, Nomdedeu, J, et al. Typical CBFbeta/MYH11 fusion due to insertion of the 3′-MYH11 gene into 16q22 in acute monocytic leukemia with normal chromosomes 16 and trisomies 8 and 22. Cancer Genet Cytogenet 2000;123:137–139.CrossRefGoogle ScholarPubMed
Bullinger, L, Rucker, FG, Kurz, S, et al. Gene-expression profiling identifies distinct subclasses of core binding factor acute myeloid leukemia. Blood 2007;110:1291–1300.CrossRefGoogle ScholarPubMed
Iwanaga, E, Nanri, T, Matsuno, N, et al. A JAK2-V617F activating mutation in addition to KIT and FLT3 mutations is associated with clinical outcome in patients with t(8;21)(q22;q22) acute myeloid leukemia. Haematologica 2009;94:433–435.CrossRefGoogle Scholar
Shimada, A, Taki, T, Tabuchi, K, et al. KIT mutations, and not FLT3 internal tandem duplication, are strongly associated with a poor prognosis in pediatric acute myeloid leukemia with t(8;21): a study of the Japanese Childhood AML Cooperative Study Group. Blood 2006;107:1806–1809.CrossRefGoogle ScholarPubMed
Sanz, MA, Grimwade, D, Tallman, MS, et al. Management of acute promyelocytic leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2009;113:1875–1891.CrossRefGoogle Scholar
Ortega, JJ, Madero, L, Martin, G, et al. Treatment with all-trans-retinoic acid and anthracycline monochemotherapy for children with acute promyelocytic leukemia: a multicenter study by the PETHEMA Group. J Clin Oncol 2005;23:7632–7640.CrossRefGoogle ScholarPubMed
Gregory, J, Kim, H, Alonzo, T, et al. Treatment of children with acute promyelocytic leukemia: results of the first North American Intergroup trial INT0129. Pediatr Blood Cancer 2009;53:1005–1010.CrossRefGoogle ScholarPubMed
Wang, ZY, Chen, Z. Acute promyelocytic leukemia: from highly fatal to highly curable. Blood 2008;111:2505–2515.CrossRefGoogle ScholarPubMed
Grimwade, D, Biondi, A, Mozziconacci, MJ, et al. Characterization of acute promyelocytic leukemia cases lacking the classic t(15;17): results of the European Working Party. Groupe Francais de Cytogenetique Hematologique, Groupe de Francais d'Hematologie Cellulaire, UK Cancer Cytogenetics Group and BIOMED 1 European Community-Concerted Action “Molecular Cytogenetic Diagnosis in Haematological Malignancies.” Blood 2000;96:1297–1308.Google Scholar
Rolston, R, Weck, KE, Tersak, JM, et al. New cytogenetic variant, insertion (15;17)(q22;q12q21), in an adolescent with acute promyelocytic leukemia. Cancer Genet Cytogenet 2002;134:55–59.CrossRefGoogle Scholar
Dolan, M, Peterson, B, Hirsch, B. Array-based comparative genomic hybridization characterizes a deletion associated with a t(15;17) in acute promyelocytic leukemia. Am J Clin Pathol 2008;130:818–823.CrossRefGoogle Scholar
Wang, HY, Ding, J, Vasef, MA, Wilson, KS. A bcr3/short form PML-RARalpha transcript in an acute promyelocytic leukemia resulted from a derivative chromosome 17 due to submicroscopic insertion of the PML gene into the RARalpha locus. Am J Clin Pathol 2009;131:64–71.CrossRefGoogle Scholar
Mozziconacci, MJ, Liberatore, C, Brunel, V, et al. In vitro response to all-trans retinoic acid of acute promyelocytic leukemias with nonreciprocal PML/RARA or RARA/PML fusion genes. Genes Chromosomes Cancer 1998;22:241–250.3.0.CO;2-R>CrossRefGoogle ScholarPubMed
Kim, M, Lim, J, Kim, Y, et al. The genetic characterization of acute promyelocytic leukemia with cryptic t(15;17) including a new recurrent additional cytogenetic abnormality i(17)(q10). Leukemia 2008;22:881–883.CrossRefGoogle Scholar
Kato, T, Hangaishi, A, Ichikawa, M, et al. A new three-way variant t(15;22;17)(q22;q11.2;q21) in acute promyelocytic leukemia. Int J Hematol 2009;89:204–208.CrossRefGoogle Scholar
Redner, RL, Contis, LC, Craig, F, et al. A novel t(3;17)(p25;q21) variant translocation of acute promyelocytic leukemia with rearrangement of the RARA locus. Leukemia 2006;20:376–379.CrossRefGoogle Scholar
Catalano, A, Dawson, MA, Somana, K, et al. The PRKAR1A gene is fused to RARA in a new variant acute promyelocytic leukemia. Blood 2007;110:4073–4076.CrossRefGoogle Scholar
Kondo, T, Mori, A, Darmanin, S, et al. The seventh pathogenic fusion gene FIP1L1-RARA was isolated from a t(4;17)-positive acute promyelocytic leukemia. Haematologica 2008;93:1414–1416.CrossRefGoogle Scholar
Wells, RA, Catzavelos, C, Kamel-Reid, S. Fusion of retinoic acid receptor alpha to NuMA, the nuclear mitotic apparatus protein, by a variant translocation in acute promyelocytic leukaemia. Nat Genet 1997;17:109–113.CrossRefGoogle ScholarPubMed
Redner, RL. Variations on a theme: the alternate translocations in APL. Leukemia 2002;16:1927–1932.CrossRefGoogle ScholarPubMed
He, LZ, Bhaumik, M, Tribioli, C, et al. Two critical hits for promyelocytic leukemia. Mol Cell 2000;6:1131–1141.CrossRefGoogle ScholarPubMed
Cox, MC, Panetta, P, Lo-Coco, F, et al. Chromosomal aberration of the 11q23 locus in acute leukemia and frequency of MLL gene translocation: results in 378 adult patients. Am J Clin Pathol 2004;122:298–306.CrossRefGoogle ScholarPubMed
Creutzig, U, Buchner, T, Sauerland, MC, et al. Significance of age in acute myeloid leukemia patients younger than 30 years: a common analysis of the pediatric trials AML-BFM 93/98 and the adult trials AMLCG 92/99 and AMLSG HD93/98A. Cancer 2008;112:562–571.CrossRefGoogle ScholarPubMed
Pui, CH, Behm, FG, Raimondi, SC, et al. Secondary acute myeloid leukemia in children treated for acute lymphoid leukemia. N Engl J Med 1989;321:136–142.CrossRefGoogle ScholarPubMed
Balgobind, BV, Raimondi, SC, Harbott, J, et al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood 2009;114:2489–2496.CrossRefGoogle ScholarPubMed
Mathew, S, Behm, F, Dalton, J, Raimondi, S. Comparison of cytogenetics, Southern blotting, and fluorescence in situ hybridization as methods for detecting MLL gene rearrangements in children with acute leukemia and with 11q23 abnormalities. Leukemia 1999;13:1713–1720.CrossRefGoogle ScholarPubMed
Konig, M, Reichel, M, Marschalek, R, Haas, OA, Strehl, S. A highly specific and sensitive fluorescence in situ hybridization assay for the detection of t(4;11)(q21;q23) and concurrent submicroscopic deletions in acute leukaemias. Br J Haematol 2002;116:758–764.CrossRefGoogle Scholar
Barber, KE, Ford, AM, Harris, RL, Harrison, CJ, Moorman, AV. MLL translocations with concurrent 3′ deletions: interpretation of FISH results. Genes Chromosomes Cancer 2004;41:266–271.CrossRefGoogle ScholarPubMed
Bacher, U, Schnittger, S, Kern, W, et al. The incidence of submicroscopic deletions in reciprocal translocations is similar in acute myeloid leukemia, BCR-ABL positive acute lymphoblastic leukemia, and chronic myeloid leukemia. Haematologica 2005;90:558–559.Google ScholarPubMed
Moon, HW, Chang, YH, Kim, TY, et al. Incidence of submicroscopic deletions vary according to disease entities and chromosomal translocations in hematologic malignancies: investigation by fluorescence in situ hybridization. Cancer Genet Cytogenet 2007;175:166–168.CrossRefGoogle ScholarPubMed
Krauter, J, Wagner, K, Schafer, I, et al. Prognostic factors in adult patients up to 60 years old with acute myeloid leukemia and translocations of chromosome band 11q23: individual patient data-based meta-analysis of the German Acute Myeloid Leukemia Intergroup. J Clin Oncol 2009;27:3000–3006.CrossRefGoogle ScholarPubMed
Martineau, M, Berger, R, Lillington, DM, Moorman, AV, Secker-Walker, LM. The t(6;11)(q27;q23) translocation in acute leukemia: a laboratory and clinical study of 30 cases. EU Concerted Action 11q23 Workshop participants. Leukemia 1998;12:788–791.CrossRefGoogle Scholar
Taki, T, Shibuya, N, Taniwaki, M, et al. ABI-1, a human homolog to mouse ABI-interactor 1, fuses the MLL gene in acute myeloid leukemia with t(10;11)(p11.2;q23). Blood 1998;92:1125–1130.Google Scholar
Chaplin, T, Bernard, O, Beverloo, HB, et al. The t(10;11) translocation in acute myeloid leukemia (M5) consistently fuses the leucine zipper motif of AF10 onto the HRX gene. Blood 1995;86:2073–2076.Google Scholar
van Limbergen, H, Poppe, B, Janssens, A, et al. Molecular cytogenetic analysis of 10;11 rearrangements in acute myeloid leukemia. Leukemia 2002;16:344–351.CrossRefGoogle ScholarPubMed
Stasevich, I, Utskevich, R, Kustanovich, A, et al. Translocation (10;11)(p12;q23) in childhood acute myeloid leukemia: incidence and complex mechanism. Cancer Genet Cytogenet 2006;169:114–120.CrossRefGoogle ScholarPubMed
Rowley, JD, Reshmi, S, Sobulo, O, et al. All patients with the t(11;16)(q23;p13.3) that involves MLL and CBP have treatment-related hematologic disorders. Blood 1997;90:535–541.Google Scholar
Ida, K, Kitabayashi, I, Taki, T, et al. Adenoviral E1A-associated protein p300 is involved in acute myeloid leukemia with t(11;22)(q23;p13). Blood 1997;90:4699–4704.Google Scholar
Gamou, T, Kitamura, E, Hosoda, F, et al. The partner gene of AML1 in t(16;21) myeloid malignancies is a novel member of the MTG8(ETO) family. Blood 1998;91:4028–4037.Google Scholar
Caligiuri, MA, Schichman, SA, Strout, MP, et al. Molecular rearrangement of the ALL-1 gene in acute myeloid leukemia without cytogenetic evidence of 11q23 chromosomal translocations. Cancer Res 1994;54:370–373.Google ScholarPubMed
Carroll, AJ, Civin, S, Schneider, NR, et al. The t(1;22)(p13;q13) is nonrandom and restricted to infants with acute megakaryoblastic leukemia: a Pediatric Oncology Group Study. Blood 1991;78:748–752.Google Scholar
Hsiao, HH, Yang, MY, Liu, YC, et al. RBM15-MKL1 (OTT-MAL) fusion transcript in an adult acute myeloid leukemia patient. Am J Hematol 2005;79:43–45.CrossRefGoogle Scholar
Duchayne, E, Fenneteau, O, Pages, MP, et al. Acute megakaryoblastic leukaemia: a national clinical and biological study of 53 adult and childhood cases by the Groupe Francais d'Hematologie Cellulaire (GFHC). Leuk Lymphoma 2003;44:49–58.CrossRefGoogle Scholar
Mercher, T, Coniat, MB, Monni, R, et al. Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia. Proc Natl Acad Sci USA 2001;98:5776–5779.CrossRefGoogle Scholar
Ma, Z, Morris, SW, Valentine, V, et al. Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia. Nat Genet 2001;28:220–221.CrossRefGoogle Scholar
Mitani, K, Ogawa, S, Tanaka, T, et al. Generation of the AML1-EVI-1 fusion gene in the t(3;21)(q26;q22) causes blastic crisis in chronic myelocytic leukemia. EMBO J 1994;13:504–510.Google Scholar
Poppe, B, Dastugue, N, Vandesompele, J, et al. EVI1 is consistently expressed as principal transcript in common and rare recurrent 3q26 rearrangements. Genes Chromosomes Cancer 2006;45:349–356.CrossRefGoogle ScholarPubMed
De Weer, A, Speleman, F, Cauwelier, B, et al. EVI1 overexpression in t(3;17) positive myeloid malignancies results from juxtaposition of EVI1 to the MSI2 locus at 17q22. Haematologica 2008;93:1903–1907.CrossRefGoogle Scholar
Madrigal, I, Carrio, A, Gomez, C, et al. Fluorescence in situ hybridization studies using BAC clones of the EVI1 locus in hematological malignancies with 3q rearrangements. Cancer Genet Cytogenet 2006;170:115–120.CrossRefGoogle ScholarPubMed
Bobadilla, D, Enriquez, EL, Alvarez, G, et al. An interphase fluorescence in situ hybridisation assay for the detection of 3q26.2/EVI1 rearrangements in myeloid malignancies. Br J Haematol 2007;136:806–813.CrossRefGoogle ScholarPubMed
Raimondi, SC, Dube, ID, Valentine, MB, et al. Clinicopathologic manifestations and breakpoints of the t(3;5) in patients with acute nonlymphocytic leukemia. Leukemia 1989;3:42–47.Google Scholar
Yoneda-Kato, N, Look, TA, Kirstein, MN, et al. The t(3;5)(q25.1;q34) of myelodysplastic syndrome and acute myeloid leukemia produces a novel fusion gene, NPM-MLF1. Oncogene 1996;12:265–275.Google Scholar
Sevilla, J, Fernandez-Plaza, S, Lassaletta, A, et al. Early acute myeloblastic leukemia treatment for childhood myelodysplastic syndrome with t(3;5) (NPM/MLF1). J Pediatr Hematol Oncol 2007;29:839–840.CrossRefGoogle Scholar
Jaju, RJ, Haas, OA, Neat, M, et al. A new recurrent translocation, t(5;11)(q35;p15.5), associated with del(5q) in childhood acute myeloid leukemia. The UK Cancer Cytogenetics Group (UKCCG). Blood 1999;94:773–780.Google Scholar
Jaju, RJ, Fidler, C, Haas, OA, et al. A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia. Blood 2001;98:1264–1267.CrossRefGoogle Scholar
Brown, J, Jawad, M, Twigg, SR, et al. A cryptic t(5;11)(q35;p15.5) in 2 children with acute myeloid leukemia with apparently normal karyotypes, identified by a multiplex fluorescence in situ hybridization telomere assay. Blood 2002;99:2526–2531.CrossRefGoogle Scholar
Panarello, C, Rosanda, C, Morerio, C. Cryptic translocation t(5;11)(q35;p15.5) with involvement of the NSD1 and NUP98 genes without 5q deletion in childhood acute myeloid leukemia. Genes Chromosomes Cancer 2002;35:277–281.CrossRefGoogle Scholar
Cerveira, N, Correia, C, Doria, S, et al. Frequency of NUP98-NSD1 fusion transcript in childhood acute myeloid leukaemia. Leukemia 2003;17:2244–2247.CrossRefGoogle ScholarPubMed
Nebral, K, Konig, M, Schmidt, HH, et al. Screening for NUP98 rearrangements in hematopoietic malignancies by fluorescence in situ hybridization. Haematologica 2005;90:746–752.Google ScholarPubMed
Slovak, ML, Gundacker, H, Bloomfield, CD, et al. A retrospective study of 69 patients with t(6;9)(p23;q34) AML emphasizes the need for a prospective, multicenter initiative for rare “poor prognosis” myeloid malignancies. Leukemia 2006;20:1295–1297.CrossRefGoogle Scholar
Ageberg, M, Drott, K, Olofsson, T, Gullberg, U, Lindmark, A. Identification of a novel and myeloid specific role of the leukemia-associated fusion protein DEK-NUP214 leading to increased protein synthesis. Genes Chromosomes Cancer 2008;47:276–287.CrossRefGoogle ScholarPubMed
Esteyries, S, Perot, C, Adelaide, J, et al. NCOA3, a new fusion partner for MOZ/MYST3 in M5 acute myeloid leukemia. Leukemia 2008;22:663–665.CrossRefGoogle ScholarPubMed
Gervais, C, Murati, A, Helias, C, et al. Acute myeloid leukaemia with 8p11 (MYST3) rearrangement: an integrated cytologic, cytogenetic and molecular study by the groupe francophone de cytogenetique hematologique. Leukemia 2008;22:1567–1575.CrossRefGoogle ScholarPubMed
Borrow, J, Stanton, VP, Jr., Andresen, JM, et al. The translocation t(8;16)(p11;q13) of acute myeloid leukaemia fuses a putative acetyltransferase to the CREB-binding protein. Nat Genet 1996;14:33–41.CrossRefGoogle Scholar
Carapeti, M, Aguiar, RC, Goldman, JM, Cross, NC. A novel fusion between MOZ and the nuclear receptor coactivator TIF2 in acute myeloid leukemia. Blood 1998;91:3127–3133.Google ScholarPubMed
Tasaka, T, Nagai, M, Matsuhashi, Y, et al. Secondary acute monocytic leukemia with a translocation t(8;22)(p11;q13). Haematologica 2002;87: ECR19.Google Scholar
Crowley, JA, Wang, Y, Rapoport, AP, Ning, Y. Detection of MOZ-CBP fusion in acute myeloid leukemia with 8;16 translocation. Leukemia 2005;19:2344–2345.CrossRefGoogle ScholarPubMed
Camos, M, Esteve, J, Jares, P, et al. Gene expression profiling of acute myeloid leukemia with translocation t(8;16)(p11;p13) and MYST3-CREBBP rearrangement reveals a distinctive signature with a specific pattern of HOX gene expression. Cancer Res 2006;66:6947–6954.CrossRefGoogle Scholar
Murati, A, Gervais, C, Carbuccia, N, et al. Genome profiling of acute myelomonocytic leukemia: alteration of the MYB locus in MYST3-linked cases. Leukemia 2009;23:85–94.CrossRefGoogle ScholarPubMed
Haferlach, T, Kohlmann, A, Klein, HU, et al. AML with translocation t(8;16)(p11;p13) demonstrates unique cytomorphological, cytogenetic, molecular and prognostic features. Leukemia 2009;23:934–943.CrossRefGoogle Scholar
Glassman, AB, Hayes, KJ. Translocation (11;16)(q23;p13) acute myelogenous leukemia and myelodysplastic syndrome. Ann Clin Lab Sci 2003;33:285–288.Google ScholarPubMed
Caudell, D, Aplan, PD. The role of CALM-AF10 gene fusion in acute leukemia. Leukemia 2008;22:678–685.CrossRefGoogle ScholarPubMed
Peniket, A, Wainscoat, J, Side, L, et al. Del (9q) AML: clinical and cytological characteristics and prognostic implications. Br J Haematol 2005;129:210–220.CrossRefGoogle ScholarPubMed
Frohling, S, Schlenk, RF, Krauter, J, et al. Acute myeloid leukemia with deletion 9q within a noncomplex karyotype is associated with CEBPA loss-of-function mutations. Genes Chromosomes Cancer 2005;42:427–432.CrossRefGoogle ScholarPubMed
Lam, DH, Aplan, PD. NUP98 gene fusions in hematologic malignancies. Leukemia 2001;15:1689–1695.CrossRefGoogle ScholarPubMed
Romana, SP, Radford-Weiss, I, Ben, AR, et al. NUP98 rearrangements in hematopoietic malignancies: a study of the Groupe Francophone de Cytogenetique Hematologique. Leukemia 2006;20:696–706.CrossRefGoogle ScholarPubMed
Reader, JC, Meekins, JS, Gojo, I, Ning, Y. A novel NUP98-PHF23 fusion resulting from a cryptic translocation t(11;17)(p15;p13) in acute myeloid leukemia. Leukemia 2007;21:842–844.CrossRefGoogle Scholar
Jankovic, D, Gorello, P, Liu, T, et al. Leukemogenic mechanisms and targets of a NUP98/HHEX fusion in acute myeloid leukemia. Blood 2008;111:5672–5682.CrossRefGoogle ScholarPubMed
Gorello, P, Brandimarte, L, La, SR, et al. t(3;11)(q12;p15)/NUP98-LOC348801 fusion transcript in acute myeloid leukemia. Haematologica 2008;93:1398–1401.CrossRefGoogle Scholar
Tosi, S, Harbott, J, Teigler-Schlegel, A, et al. t(7;12)(q36;p13), a new recurrent translocation involving ETV6 in infant leukemia. Genes Chromosomes Cancer 2000;29:325–332.3.0.CO;2-9>CrossRefGoogle Scholar
Slater, RM, von Drunen, E, Kroes, WG, et al. t(7;12)(q36;p13) and t(7;12)(q32;p13): translocations involving ETV6 in children 18 months of age or younger with myeloid disorders. Leukemia 2001;15:915–920.CrossRefGoogle ScholarPubMed
von Bergh, AR, van Drunen, E, van Wering, ER, et al. High incidence of t(7;12)(q36;p13) in infant AML but not in infant ALL, with a dismal outcome and ectopic expression of HLXB9. Genes Chromosomes Cancer 2006;45:731–739.CrossRefGoogle Scholar
Beverloo, HB, Panagopoulos, I, Isaksson, M, et al. Fusion of the homeobox gene HLXB9 and the ETV6 gene in infant acute myeloid leukemias with the t(7;12)(q36;p13). Cancer Res 2001;61:5374–5377.Google Scholar
Lannon, CL, Sorensen, PH. ETV6–NTRK3: a chimeric protein tyrosine kinase with transformation activity in multiple cell lineages. Semin Cancer Biol 2005;15:215–223.CrossRefGoogle ScholarPubMed
Vieira, L, Marques, B, Ambrosio, AP, et al. TEL and MN1 fusion in myelodysplastic syndrome: new evidence for a therapy-related event. Br J Haematol 2000;110:238–239.CrossRefGoogle ScholarPubMed
, Barjesteh van, Waalwijk vanDoorn-Khosrovani, S, Spensberger, D, de Knegt, Y, et al. Somatic heterozygous mutations in ETV6 (TEL) and frequent absence of ETV6 protein in acute myeloid leukemia. Oncogene 2005;24:4129–4137.Google Scholar
Choi, HW, Shin, MG, Sawyer, JR, et al. Unusual type of TLS/FUS-ERG chimeric transcript in a pediatric acute myelocytic leukemia with 47,XX,+10,t(16;21)(p11;q22). Cancer Genet Cytogenet 2006;167:172–176.CrossRefGoogle Scholar
Kondoh, K, Nakata, Y, Furuta, T, et al. A pediatric case of secondary leukemia associated with t(16;21)(q24;q22) exhibiting the chimeric AML1-MTG16 gene. Leuk Lymphoma 2002;43:415–420.CrossRefGoogle Scholar
Haferlach, C, Dicker, F, Herholz, H, et al. Mutations of the TP53 gene in acute myeloid leukemia are strongly associated with a complex aberrant karyotype. Leukemia 2008;22:1539–1541.CrossRefGoogle ScholarPubMed
Bowen, D, Groves, MJ, Burnett, AK, et al. TP53 gene mutation is frequent in patients with acute myeloid leukemia and complex karyotype, and is associated with very poor prognosis. Leukemia 2009;23:203–206.CrossRefGoogle ScholarPubMed
Seifert, H, Mohr, B, Thiede, C, et al. The prognostic impact of 17p (p53) deletion in 2272 adults with acute myeloid leukemia. Leukemia 2009;23:656–663.CrossRefGoogle ScholarPubMed
Nahi, H, Selivanova, G, Lehmann, S, et al. Mutated and non-mutated TP53 as targets in the treatment of leukaemia. Br J Haematol 2008;141: 445–453.CrossRefGoogle ScholarPubMed
Brezinova, J, Zemanova, Z, Ransdorfova, S, et al. Prognostic significance of del(20q) in patients with hematological malignancies. Cancer Genet Cytogenet 2005;160:188–192.CrossRefGoogle ScholarPubMed
Asou, N, Yanagida, M, Huang, L, et al. Concurrent transcriptional deregulation of AML1/RUNX1 and GATA factors by the AML1-TRPS1 chimeric gene in t(8;21)(q24;q22) acute myeloid leukemia. Blood 2007;109:4023–4027.CrossRefGoogle Scholar
Roche-Lestienne, C, Deluche, L, Corm, S, et al. RUNX1 DNA-binding mutations and RUNX1-PRDM16 cryptic fusions in BCR-ABL+ leukemias are frequently associated with secondary trisomy 21 and may contribute to clonal evolution and imatinib resistance. Blood 2008;111:3735–3741.CrossRefGoogle Scholar
Sorour, Y, Dalley, CD, Snowden, JA, Cross, NC, Reilly, JT. Acute myeloid leukaemia with associated eosinophilia: justification for FIP1L1-PDGFRA screening in cases lacking the CBFB-MYH11 fusion gene. Br J Haematol 2009;146:225–227.CrossRefGoogle ScholarPubMed
Cross, NC, Reiter, A. Tyrosine kinase fusion genes in chronic myeloproliferative diseases. Leukemia 2002;16:1207–1212.CrossRefGoogle ScholarPubMed
Apperley, JF, Gardembas, M, Melo, JV, et al. Response to imatinib mesylate in patients with chronic myeloproliferative diseases with rearrangements of the platelet-derived growth factor receptor beta. N Engl J Med 2002;347: 481–487.CrossRefGoogle ScholarPubMed
David, M, Cross, NC, Burgstaller, S, et al. Durable responses to imatinib in patients with PDGFRB fusion gene-positive and BCR-ABL-negative chronic myeloproliferative disorders. Blood 2007;109:61–64.CrossRefGoogle ScholarPubMed
Walz, C, Metzgeroth, G, Haferlach, C, et al. Characterization of three new imatinib-responsive fusion genes in chronic myeloproliferative disorders generated by disruption of the platelet-derived growth factor receptor beta gene. Haematologica 2007;92:163–169.CrossRefGoogle ScholarPubMed
Hidalgo-Curtis, C, Apperley, JF, Stark, A, et al. Fusion of PDGFRB to two distinct loci at 3p21 and a third at 12q13 in imatinib-responsive myeloproliferative neoplasms. Br J Haematol 2010;148:268–273.CrossRefGoogle Scholar
Zhang, WW, Habeebu, S, Sheehan, AM, et al. Molecular monitoring of 8p11 myeloproliferative syndrome in an infant. J Pediatr Hematol Oncol 2009;31:879–883.CrossRefGoogle ScholarPubMed
Soler, G, Nusbaum, S, Varet, B, et al. LRRFIP1, a new FGFR1 partner gene associated with 8p11 myeloproliferative syndrome. Leukemia 2009;23:1359–1361.CrossRefGoogle ScholarPubMed
Goradia, A, Bayerl, M, Cornfield, D. The 8p11 myeloproliferative syndrome: review of literature and an illustrative case report. Int J Clin Exp Pathol 2008;1:448–456.Google ScholarPubMed

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