Molecular cytogenetics in acute myeloid leukemia in adult patients: practical implications

Abstract

Throughout the last 50 years, cytogenetic analyses of pretreatment bone marrow and/or blood samples from patients diagnosed with acute myeloid leukemia (AML) revealed a large number of recurring chromosome aberrations, both structural and numerical. Using standard banding methods and, more recently, molecular cytogenetic techniques such as fluorescence in situ hybridization, spectral karyotyping, multiplex fluorescence in situ hybridization and comparative genomic hybridization, cytogenetic investigations detect acquired abnormalities that, together with submicroscopic gene mutations and changes in gene expression, strongly influence clinical features and prognosis of AML patients. Selected reciprocal translocations and inversions and their molecular counterparts, as well as a number of unbalanced chromosome abnormalities, are used, together with BM morphology, immunophenotype and clinical characteristics, to define separate AML entities in the World Health Organization Classification of Haematolymphoid Tumours. Moreover, cytogenetic findings (and specific gene mutations) are being used in genetic-risk classifications, such as the 2022 European LeukemiaNet classification, that separate patients into broad prognostic categories: favorable, intermediate and adverse, which are useful in the management of patients with AML. In this article, I review the present data on recurrent chromosome rearrangements in AML and on correlations between cytogenetic findings and clinical features and treatment outcomes of adult patients diagnosed with AML.

Sex-associated differences in frequencies and prognostic impact of recurrent genetic alterations in adult acute myeloid leukemia (Alliance, AMLCG)

“…The discovery of recurrent cytogenetic and molecular genetic alterations has improved our understanding of AML biology and resulted in the routine use of pre-treatment genetic alterations for risk strati cation. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] However, genetic changes should not be assessed in isolation, because their effects may be in uenced by such factors as patients age 1,2,9,20 and/or racial-ethnic identity. 21,22 Whereas female and male patients with AML share the vast majority of genetic information, except for at least 26 protein-coding genes located on the Y chromosome, large-scale genomic studies of health and disease have revealed profound differences in sex-biased gene-regulatory networks 31 and splicing events 32 contributing to phenotypic sex differences.…”

“…1,2 Several pretreatment factors, both diseaseand patient-speci c, affect prognosis of AML patients. [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19] The former include recurrent cytogenetic ndings [3][4][5][6][7][8][9][10][11] and gene mutations [12][13][14][15][16][17][18][19] at diagnosis, whereas increasing age is a well-known patientspeci c predictor of worse survival. 1,2,9,20 The incidence of acquired cytogenetic and molecular alterations and their prognostic impact vary by age 9 and racial-ethnic identity.…”

Global disease burden and trends of leukemia attributable to occupational risk from 1990 to 2019: An observational trend study

“…French-American-British (FAB) classification ( 40 ) and MICM classification (Morphology, Immunology, Cytogenetics, and Molecular) classification ( 41 ). Meanwhile, the diagnostic criteria for leukemia have also changed ( 42 , 43 ). In terms of the countries and regions' distribution of these two kinds of leukemia, in Mexico and Latin America, the age-standardized DALYs and death rates were the highest, possibly because of the most common of these two types of leukemia in young adults and regional economic development.…”

Outcome prediction by the 2022 European LeukemiaNet genetic-risk classification for adults with acute myeloid leukemia: an Alliance study

“…Pretreatment cytogenetic findings were first to be used to prognostically stratify patients with acute myeloid leukemia (AML) [1][2][3][4][5][6][7][8][9]. Subsequently, several gene mutations were demonstrated to provide additional prognostic information [10][11][12][13][14][15][16][17][18][19].…”