Somatic Mutations Drive Specific, but Reversible, Epigenetic Heterogeneity States in AML.
Cancer Discov 2020 Dec; 10(12):1934-1949
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
Li, Sheng; Chen, Xiaowen; Wang, Jiahui; Meydan, Cem; Glass, Jacob L; Shih, Alan H; Delwel, Ruud; Levine, Ross L; Mason, Christopher E; and Melnick, Ari M, "Somatic Mutations Drive Specific, but Reversible, Epigenetic Heterogeneity States in AML." (2020). Faculty Research 2020. 243.