Title

Somatic Mutations Drive Specific, but Reversible, Epigenetic Heterogeneity States in AML.

Document Type

Article

Publication Date

12-2020

Keywords

JGM, JAXCC

JAX Source

Cancer Discov 2020 Dec; 10(12):1934-1949

Volume

10

Issue

12

First Page

1934

Last Page

1949

ISSN

2159-8290

PMID

32938585

DOI

https://doi.org/10.1158/2159-8290.cd-19-0897

Grant

GM133562; CA034196

Abstract

Epigenetic allele diversity is linked to inferior prognosis in acute myeloid leukemia (AML). However, the source of epiallele heterogeneity in AML is unknown. Herein we analyzed epiallele diversity in a genetically and clinically annotated AML cohort. Notably, AML driver mutations linked to transcription factors and favorable outcome are associated with epigenetic destabilization in a defined set of susceptible loci. In contrast, AML subtypes linked to inferior prognosis manifest greater abundance and highly stochastic epiallele patterning. We report an epiallele outcome classifier supporting the link between epigenetic diversity and treatment failure. Mouse models with

Comments

We thank Stephen Sampson from The Jackson Laboratory for editing this manuscript. The authors thank members of Li laboratory and Melnick laboratory for discussion, and the technique support of The Jackson Laboratory Computer Sciences team and Research Informatics Technology team.

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