Journal
CANCER CELL
Volume 29, Issue 6, Pages 922-934Publisher
CELL PRESS
DOI: 10.1016/j.ccell.2016.05.003
Keywords
-
Categories
Funding
- Robert and Janice McNair Foundation
- CPRIT [RP110028, RP110471, RP150292]
- NIH [DK092883, CA183252, CA193466, HG007538]
- Samuel Waxman Cancer Research Foundation
- Adrienne Helis Malvin Foundation
- Biotechnology and Biological Sciences Research Council [BB/I00050X/1] Funding Source: researchfish
- Cancer Research UK [12765] Funding Source: researchfish
- Medical Research Council [MC_PC_12009] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0512-10079] Funding Source: researchfish
- BBSRC [BB/I00050X/1] Funding Source: UKRI
Ask authors/readers for more resources
DNMT3A, the gene encoding the de novo DNA methyltransferase 3A, is among the most frequently mutated genes in hematologic malignancies. However, the mechanisms through which DNMT3A normally suppresses malignancy development are unknown. Here, we show that DNMT3A loss synergizes with the FLT3 internal tandem duplication in a dose-influenced fashion to generate rapid lethal lymphoid or myeloid leukemias similar to their human counterparts. Loss of DNMT3A leads to reduced DNA methylation, predominantly at hematopoietic enhancer regions in both mouse and human samples. Myeloid and lymphoid diseases arise from transformed murine hematopoietic stem cells. Broadly, our findings support a role for DNMT3A as a guardian of the epigenetic state at enhancer regions, critical for inhibition of leukemic transformation.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available