Skip to main content Accessibility help
  • Get access
    Check if you have access via personal or institutional login
  • Cited by 1
  • Print publication year: 2010
  • Online publication date: December 2010

4 - Cytogenetics

from Part 1 - Diagnostic techniques



For many years cytogenetic analysis has provided the gold standard tool for basic genetic diagnosis in hematological malignancies. Although resolution is somewhat limited, it provides a global analysis of the entire genome. In recent years a range of fluorescence in situ hybridization (FISH) and high resolution array-based techniques have become integrated into the broader field of cytogenetics, which have provided complementary rather than replacement approaches. They have identified novel and submicroscopic genetic changes, which need to be considered alongside the traditional karyotype.

A number of chromosomal abnormalities provide the definitive diagnosis of a specific type of leukemia. The best known examples include the association of the Philadelphia chromosome (Ph), arising from the translocation, t(9;22)(q34;q11), with chronic myelogenous leukemia (CML) and the translocation, t(15;17)(q22;q21), with acute promyelocytic leukemia (APL). Of particular interest is the strong link between certain abnormalities and outcome, which are used to determine the risk stratification of patients for treatment. For example, the Ph and near haploidy (< 30 chromosomes) are associated with a poor prognosis in childhood acute lymphoblastic leukemia (ALL) and patients with these abnormalities are treated as high risk. Other genetic abnormalities are associated with a favorable outcome, e.g. core binding acute myeloid leukemias (AML) with chromosomal rearrangements t(8;21)(q22;q22) and inversion of chromosome 16, inv(16)(p13q22)/t(16;16)(p13;q22), and childhood ALL with hyperdiploidy (51–65 chromosomes) and t(12;21)(p13;q22). An increasing number of specific gene mutations are being described in the acute leukemias and myeloproliferative neoplasms.

,World Health Organization. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissue.Lyon: IARC Press; 2008.
,ISCN. An International System for Human Cytogenetic Nomenclature. Shaffer, LG, Slovak, ML, Campbell, LJ (eds.). Basel: S. Karger; 2009.
Greaves, M.In utero origins of childhood leukaemia. Early Hum Dev 2005;81:123–9.
Harrison, CJ, Johansson, B.Acute lymphoblastic leukaemia. In Heim, S, Mitelman, F (eds.), Cancer Cytogenetics, 3rd edn. Hoboken, NJ: John Wiley and Son Inc.; 2009.
Hong, D, Gupta, R, Ancliff, Pet al. Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia. Science 2008;319:336–9.
Harewood, L, Robinson, H, Harris, Ret al. Amplification of AML1 on a duplicated chromosome 21 in acute lymphoblastic leukemia: a study of 20 cases. Leukemia 2003;17:547–53.
Moorman, AV, Richards, SM, Robinson, HMet al. Prognosis of children with acute lymphoblastic leukemia (ALL) and intrachromosomal amplification of chromosome 21 (iAMP21). Blood 2007;109:2327–30.
Privitera, E, Kamps, MP, Hayashi, Yet al. Different molecular consequences of the 1;19 chromosomal translocation in childhood B-cell precursor acute lymphoblastic leukemia. Blood 1992;79:1781–8.
Hunger, SP. Chromosomal translocations involving the E2A gene in acute lymphoblastic leukemia: clinical features and molecular pathogenesis. Blood 1996;87:1211–24.
Barber, KE, Harrison, CJ, Broadfield, ZJet al. Molecular cytogenetic characterization of TCF3 (E2A)/19p13.3 rearrangements in B-cell precursor acute lymphoblastic leukemia. Genes Chromosomes Cancer 2007;46:478–86.
Grimaldi, JC, Meeker, TC. The t(5;14) chromosomal translocation in a case of acute lymphocytic leukemia joins the interleukin-3 gene to the immunoglobulin heavy chain gene. Blood 1989;73:2081–5.
Akasaka, T, Balasas, T, Russell, LJet 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;109:3451–61.
Russell, LJ, Akasaka, T, Majid, Aet al. t(6;14)(p22;q32): a new recurrent IGH@ translocation involving ID4 in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Blood 2008;111:387–91.
Russell, LJ, Castro, DG, Griffiths, Met al. A novel translocation, t(14;19)(q32;p13), involving IGH@ and the cytokine receptor for erythropoietin. Leukemia 2009;23:614–17.
Russell, LJ, Capasso, M, Vater, Iet al. Deregulated expression of cytokine receptor gene, CRLF2, is involved in lymphoid transformation in B-cell precursor acute lymphoblastic leukemia. Blood 2009;114:2688–98.
Hertzberg, L, Vendramini, E, Ganmore, Iet 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 iBFM Study Group. Blood 2010;115(5):1006–17.
Moorman, AV, Richards, SM, Martineau, Met al. Outcome heterogeneity in childhood high-hyperdiploid acute lymphoblastic leukemia. Blood 2003;102:2756–62.
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.
Harrison, CJ, Moorman, AV, Broadfield, ZJet al. Three distinct subgroups of hypodiploidy in acute lymphoblastic leukaemia. Br J Haematol 2004;125:552–9.
Mullighan, CG, Goorha, S, Radtke, Iet al. Genome-wide analysis of genetic alterations in acute lymphoblastic leukaemia. Nature 2007;446:758–64.
Mullighan, CG, Miller, CB, Radtke, Iet al. BCR-ABL1 lymphoblastic leukaemia is characterized by the deletion of Ikaros. Nature 2008;453:110–14.
Mullighan, C, Downing, J.Ikaros and acute leukemia. Leuk Lymphoma 2008;49:847–9.
Sulong, S, Moorman, AV, Irving, JAet 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;113:100–7.
Burg, M, Poulsen, TS, Hunger, SPet al. Split-signal FISH for detection of chromosome aberrations in acute lymphoblastic leukemia. Leukemia 2004;18:895–908.
Keersmaecker, K, Marynen, P, Cools, J. Genetic insights in the pathogenesis of T-cell acute lymphoblastic leukemia. Haematologica 2005;90:1116–27.
Johansson, B, Harrison, CJ.Acute myeloid leukaemia. In Heim, S, Mitelman, F (eds.). Cancer Cytogenetics, 3rd edn. Hoboken, NJ: John Wiley and Son Inc.; 2009.
Gale, RE, Green, C, Allen, Cet al. The impact of FLT3 internal tandem duplication mutant level, number, size, and interaction with NPM1 mutations in a large cohort of young adult patients with acute myeloid leukemia. Blood 2008;111:2776–84.
Harrison, CJ, Radford-Weiss, I, Ross, Fet al. Fluorescence in situ hybridization of masked t(8;21)(q22;q22) translocations. Cancer Genet Cytogenet 1999;112:15–20.
Grimwade, D, Jovanovic, JV, Hills, RKet al. Prospective minimal residual disease monitoring to predict relapse of acute promyelocytic leukemia and to direct pre-emptive arsenic trioxide therapy. J Clin Oncol 2009;27:3650–8.
Balgobind, BV, Raimondi, SC, Harbott, Jet al. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study. Blood 2009;114:2489–96.
Schoch, C, Kern, W, Kohlmann, Aet al. Acute myeloid leukemia with a complex aberrant karyotype is a distinct biological entity characterized by genomic imbalances and a specific gene expression profile. Genes Chromosomes Cancer 2005;43:227–38.
Grimwade, D, Walker, H, Oliver, Fet al., on behalf of the Medical Research Council Adult and Children's Leukaemia Working P. The importance of diagnostic cytogenetics on outcome in AML: analysis of 1,612 patients entered into the MRC AML 10 trial. Blood 1998;92:2322–33.
Jabbour, E, Koscielny, S, Sebban, Cet al. High survival rate with the LMT-89 regimen in lymphoblastic lymphoma (LL), but not in T-cell acute lymphoblastic leukemia (T-ALL). Leukemia 2006;20:814–19.
Baccarani, M, Saglio, G, Goldman, Jet al. Evolving concepts in the management of chronic myeloid leukemia: recommendations from an expert panel on behalf of the European LeukemiaNet. Blood 2006;108:1809–20.
Tefferi, A, Pardanani, A, Lim, KHet al. TET2 mutations and their clinical correlates in polycythemia vera, essential thrombocythemia and myelofibrosis. Leukemia 2009;23:905–11.