De novo acute myeloid leukemias (AML) represent a heterogeneous group of clonal hematopoietic disorders in which chromosomal abnormalities are detected in a majority of patients. At present, cytogenetic changes are recognized as important diagnostic markers and prognosis determinants. Complex karyotype changes are associated with resistance to treatment and unfavorable evolution. We report on an AML case with complex karyotype changes characterized by molecular genetic techniques (fluorescence in situ hybridization - FISH and array-based comparative genomic hybridization - array-CGH) and an extremely poor outcome. A 72 year-old female patient was admitted for genetic investigations with a clinical diagnosis of AML. Classical and molecular cytogenetic tests as well as array-CGH were performed. Complex chromosomal abnormalities were identified at diagnosis, consisting of genomic imbalances involving chromosomes 6, 7, 9, and 17. AML with complex karyotype changes is a heterogeneous disease, as a variety of genomic abnormalities are detected, involving virtually all chromosomes. The pathogenesis of AML with complex karyotype is poorly understood. The complexity of karyotypic changes in our case highlights the importance of using complementary genetic investigation in order to obtain a comprehensive view of AML genome.
1. Grimwade D, Walker H, Oliver F, Wheatley K, Harrison C, Harrison G, et al. 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.
2. Slovak ML, Kopecky KJ, Cassileth PA, Harrington DH, Theil KS, Mohamed A, et al. Karyotypic analysis predicts outcome of preremission and postremission therapy in adult acute myeloid leukemia: a Southwest Oncology Group/Eastern Cooperative Oncology Group study. Blood 2000;96:4075-83.
3. Byrd JC, Mrozek K, Dodge RK, Carroll AJ, Edwards CG, Arthur DC et al. Pretreatment cytogenetic abnormalities are predictive of induction success, cumulative incidence of relapse, and overall survival in adult patients with de novo acute myeloid leukemia: results from Cancer and Leukemia Group B (CALGB 8461). Blood 2002;100:4325-4336.
4. Dhoner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK et al Diagnosis and management of acute Myeloid leukemia in adults: recommandations from an international expert panel, on behalf of the European Leukemia Net. Blood 2010;115: 453-74.
5. Schnittger S, Schoch C, Kern W, Mecucci C, Tschulik C, Martelli MF et al. Nucleophosmin gene mutations are predictors of favourable prognosis in acute myelogenous leukemia with a normal karyotype. Blood 2005;106:3733-3739.
6. Steudel C, Wermke M, Schaich M, Schakel U, Illmer T, Ehninger G et al. Comparative analysis of MLL partial tandem duplication and FLT3 internal tandem duplication mutations in 956 adult patients with acute myeloid leukemia. Genes Chromosomes Cancer 2003;37:237-251.
7. Lugthart S, Van Drunen E, Van Norden Y, van Hoven A, Erpelinck CAJ, Valk PJM et al. High EVI1 levels predict adverse outcome in acute myeloid leukemia: prevalence of EVI1 over-expression and chromosome 3q26 ab- normalities underestimated. Blood 2008;111:4329-4337.
8. Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A et al. The 2008 revision of the WHO classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood 2009;114:947-951.
9. Mrozek K, Heinonen K, Bloomfield CD: Clinical importance of cytogenetics in acute myeloid leukaemia. Best Pract Res Clin Haematol 2001;14:19-47.
10. Grimwade D, Walker H, Harrison G, Oliver F, Chatters S, Harrison CJ, et al. Medical Research Council Adult LeukemiaWorking Party. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia(AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial. Blood 2001;98:1312-20.
11. Rücker FG, Bullinger L, Schwaenen C, Lipka DB, Wessendorf S, Fröhling S, et al. Disclosure of candidate genes in acute myeloid leukemia with complex karyotypes using microarray-based molecular characterization. J Clin Oncol 2006;24(24):3887-94.
12. Schoch C, Kern W, Schnittger S, Büchner T, Hiddemann W, Haferlach T. The influence of age on prognosis of de novo acute myeloid leukemia differs according to cytogenetic subgroups. Haematologica 2004; 89:1082-1090.
13. Estey E, Döhner H: Acute myeloid leukaemia. The Lancet 2006; 368(9550):1894-1907.
14. Mackinnon RN, Selan C, Zordan A, Wall M, Nandurkar H, Campbell LJ. CGH and SNP array using DNA extracted from fixed cytogenetic preparations and longterm refrigerated bone marrow specimens. Mol Cytogenet 2012;5:10.
15. Kirsch DG, Kastan MB. Tumor-suppressor p53: implications for tumor development and prognosis. J Clin Oncol 1998;16:3158-3168.
16. Rücker FG, Schlenk RF, Bullinger L, Kayser S, Teleanu V, Kett H et al. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood 2012;119(9):2114-21.
17. Harousseau JL. Acute myeloid leukemia in the elderly. Blood Rev 1998;12:145-53.
18. Dhoner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK et al. Diagnosis and management of acute Myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European Leukemia Net. Blood 2010;115: 453-74.