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
Recommended Citation
Li S,
Chen X,
Wang J,
Meydan C,
Glass J,
Shih A,
Delwel R,
Levine R,
Mason C,
Melnick A.
Somatic Mutations Drive Specific, but Reversible, Epigenetic Heterogeneity States in AML. Cancer Discov 2020 Dec; 10(12):1934-1949
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.