Role of genotype-based approach in the clinical management of adult acute myeloid leukemia with normal cytogenetics

Acute myeloid leukemia (AML) is the most common form of acute leukemia affecting adults. Although it is a complex disease driven by numerous genetic and epigenetic abnormalities, nearly 50% of patients exhibit a normal karyotype (CNAML) with an intermediate cytogenetic risk. However, a widespread genomic analysis has recently shown the recurrence of genomic aberrations in this category (mutations of FLT3, CEBPA, NPM1, RUNX1, TET2, IDH1/2, DNMT3A, ASXL1, MLL and WT1) thus revealing its marked genomic heterogeneity. In this perspective, a global gene expression analysis of AML patients provides an independent prognostic marker to categorize each patient into clinicpathologic subgroups based on its molecular genetic defects. Consistently such classification, taking into account the uniqueness of each AML patient, furnishes an individualized treatment approach leading a step closer to personalized medicine. Overall the genomewide analysis of AML patients, by providing novel insights into biology of this tumor, furnishes accurate prognostic markers as well as useful tools for selecting the most appropriate treatment option. Moreover it provides novel therapeutic targets useful to enhance efficacy of the current antiAML therapeutics. Here we describe the prognostic relevance of such new genetic data and discuss how this approach can be used to improve survival and treatment of AML patients. (C) 2014 Elsevier Ltd. All rights reserved.