Cytogenetic abnormalities in adult non-promyelocytic acute myeloid leukemia: a concise review.
ABSTRACT Cytogenetic abnormalities are found in 50-60% of newly diagnosed acute myeloid leukemia (AML) of adult patients. Cytogenetic analysis of bone marrow leukemic cells is an important pre-treatment evaluation for a correct prognostic stratification of patients, that permit to separate AML patients in three broad prognostic categories: high, intermediate and low risk. The determination of cytogenetic features of AML remains a corner stone in predicting outcome although today its use needs to be integrated by molecular and immunophenotypic data, particularly in cytogenetically normal (CN) group of patients. In this review we perform a concise description of more recurrent cytogenetic aberrations found in AML, theirs correlations with biological and clinical data and theirs strong impact with outcome of patients, useful for therapeutic decision.
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ABSTRACT: Acquired chromosome aberrations are present in the marrow of most patients with acute myeloid leukaemia (AML) at diagnosis. Cytogenetically, AML is a very heterogeneous disease with over 160 structural chromosome abnormalities observed recurrently to date. Molecular dissection of many reciprocal translocations and inversions has resulted in cloning of the genes involved in leukaemogenesis. Some recurrent aberrations and the resulting gene rearrangements, namely inv(16)/t(16;16) and CBFbeta- MYH11, t(8;21) and CBFA2-CBFA2T1, t(15;17) and PML-RARalpha, and rearrangements of band 11q23 and the MLL gene, are now used to help define distinct disease entities within AML in the new World Health Organization classification of haematological malignancies. Moreover, cytogenetic abnormalities, whether molecularly characterized or not, are among the most important, independent prognostic factors in AML, and are being used in the management of AML patients. This review presents current information on chromosome abnormalities in AML, and on associations between karyotype and clinical characteristics and outcome of AML patients.Bailliè re s Best Practice and Research in Clinical Haematology 04/2001; 14(1):19-47. · 2.81 Impact Factor
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ABSTRACT: Acute myeloid leukemia (AML) in older adults carries a poor prognosis, and the optimum treatment remains to be determined. In younger patients, treatment stratification is frequently based upon diagnostic karyotype, which was the most important prognostic factor in the UK Medical Research Council (MRC) AML10 trial. Considered here is whether karyotype is also predictive in older adults; this is done by studying 1065 cases from MRC AML11 (median age, 66 years). Three prognostic groups were distinguished on the basis of response to induction therapy and overall survival (OS). Those with t(15;17), t(8;21), or inv(16) composed the favorable risk group. Overall, these abnormalities predicted a superior complete remission (CR) rate (72%), reflecting relatively low levels of resistant disease (RD) (8%), and lower relapse risk (RR) (56%) associated with superior OS (34% at 5 years). Normal karyotype (CR, 63%; RD, 17%; RR, 78%; OS, 15%) and other noncomplex abnormalities (CR, 53%; RD, 32%; RR, 85%; OS, 10%) composed the intermediate group; while complex karyotype predicted an extremely poor prognosis (CR, 26%; RD, 56%; RR, 91%; OS, 2%). Combining MRC AML10 and AML11 (n = 2677) revealed that the most favorable changes were rarer in older patients (younger than 55 years, 24%; 55 years or older, 7%), while complex abnormalities were more common (6% vs 13%). This study suggests that hierarchical cytogenetic classification identifies biologically distinct subsets of AML that are represented in all age groups. Furthermore, it highlights the importance of karyotype as a critical independent determinant of outcome in older patients with AML, providing a potential framework for stratified treatment approaches.Blood 10/2001; 98(5):1312-20. · 9.06 Impact Factor
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ABSTRACT: The associations of cytogenetics with complete remission (CR) rates, overall survival (OS), and outcomes after CR were studied in 609 previously untreated AML patients younger than 56 years old in a clinical trial comparing 3 intensive postremission therapies: intensive chemotherapy, autologous transplantation (ABMT), or allogeneic bone marrow transplantation (alloBMT) from matched related donors. Patients were categorized into favorable, intermediate, unfavorable, and unknown cytogenetic risk groups based on pretreatment karyotypes. CR rates varied significantly (P <.0001) among the 4 groups: favorable, 84% (95% confidence interval [CI], 77%-90%); intermediate, 76% (CI, 71%-81%); unfavorable, 55% (CI, 48%-63%); and unknown, 54% (CI, 33%-74%). There was similar significant heterogeneity of OS (P <.0001), with the estimated relative risk of death from any cause being 1.50 (CI, 1.10-2.05), 3. 33 (CI, 2.43-4.55), and 2.66 (CI, 1.59-4.45) for the intermediate, unfavorable, and unknown risk groups, respectively, compared with the favorable group. In multivariate analyses, the effects of cytogenetic risk status on CR rate and OS could not be explained by other patient or disease characteristics. Among postremission patients, survival from CR varied significantly among favorable, intermediate, and unfavorable groups (P =.0003), with significant evidence of interaction (P =.017) between the effects of treatment and cytogenetic risk status on survival. Patients with favorable cytogenetics did significantly better following ABMT and alloBMT than with chemotherapy alone, whereas patients with unfavorable cytogenetics did better with alloBMT. Cytogenetic risk status is a significant factor in predicting response of AML patients to therapy; however, to tighten treatment correlates within genetically defined AML subsets, a significantly larger leukemia cytogenetic database is warranted.Blood 12/2000; 96(13):4075-83. · 9.06 Impact Factor