Array-Based Cytogenetic Approaches in Acute Myeloid Leukemia: Clinical Impact and Biological Insights

Abstract

Conventional cytogenetic studies have shown that the clinical and biological diversity of acute myeloid leukemia (AML) can be attributed, in part, to distinct chromosome aberrations, several of which are now routinely used for diagnosis, risk stratification, and outcome prediction. Although chromosome banding analysis has recently been complemented by the identification of point mutations in a growing number of hematopoiesis-associated genes, current genetic categories do not fully reflect the heterogeneity of AML. To close the gap between standard karyotyping and molecular analyses at the single-base-pair level and gain additional insight into the genetics underlying myeloid leukemogenesis, AML is increasingly being studied using genome-wide, microarray-based cytogenetic methods. These investigations have revealed that AML genomes commonly harbor acquired submicroscopic copy number alterations, even though the prevalence of most of these cryptic lesions appears to be low, as well as regions of uniparental disomy that are often associated with homozygosity of functionally relevant gene mutations. Current efforts are focusing on the application of this expanded knowledge to improve the classification of AML, develop new tools for prognostication and prediction of response to therapy, and accelerate the discovery of genes that are likely to contribute to AML pathogenesis.