Mutant DNMT3A: Teaming up to transform

摘要

The report by Ribeiro et al in this issue of Blood confirms the evolving data that DNMT3A mutations represent another common alteration in adult acute myeloid leukemia (AML) and are an important modulator of outcome. Within the past 2 years, the invention of next-generation sequencing (NGS) has revealed a plethora of previously undescribed genetic abnormalities affecting several different pathways, including mutations in IDH1 and IDH2, and DNMT3A as well as numerous less common or even patient-specific abnormalities. Clarification of the prevalence and the prognostic impact of these changes has become a critical issue in how to identify the driver lesions and in deciding which factors should be added to the set of molecular abnormalities routinely tested. In a large and well-characterized population of adult patients with AML, Ribeiro et al investigated the prevalence and prognostic impact of DNMT3A mutations. In this series, 96 of 415 patients (23 percent) carried a mutation of the gene, which ranks it among the most common changes in adult AML.