Epigenenomic and transcriptomic characterization ofNPM1-mutated CN-AML subtypes

Abstract

ABSTRACTCytogenetic normal AML withNPM1mutations forms a distinct AML entity, associated with an intermediate prognosis and a heterogeneous response to treatment. We previously described an epigenetic biomarker, defined by the level of H3K27me3 on 70kb of theHIST1cluster in patient blast DNA. This epigenetic mark separates cytogenetically normalNPM1mutAML into two groups of patients differing in their survival rate following chemotherapy. To better characterize the influence of the biomarker on disease progression, we performed transcriptomic and histone mark profiling on patient blasts according to the level of H3K27me3HIST1. Our integrated analysis revealed that the two groups of patients display differences in terms of transcriptomic, chromatin landscape and cell surface markers, which could explain the clinical difference. Our profiling revealed novel targets and therefore constitutes an (epi)transcriptomic resource forNPM1AML. It also highlights the power of epigenetic profiling to dissect the heterogeneity of a single AML genetic entity.