Mir142 loss unlocks IDH2^R140-dependent leukemogenesis through antagonistic regulation of HOX genes.

ABSTRACT: AML is a genetically heterogeneous disease and understanding how different co-occurring mutations cooperate to drive leukemogenesis will be crucial for improving diagnostic and therapeutic options for patients. MIR142 mutations have been recurrently detected in IDH-mutated AML samples. Here, we have used a mouse model to investigate the interaction between these two mutations and demonstrate a striking synergy between Mir142 loss-of-function and IDH2^R140Q, with only recipients of double mutant cells succumbing to leukemia. Transcriptomic analysis of the non-leukemic single and leukemic double mutant progenitors, isolated from these mice, suggested a novel mechanism of cooperation whereby Mir142 loss-of-function counteracts aberrant silencing of Hoxa cluster genes by IDH2^R14

SUBMITTER: Marshall A 

PROVIDER: S-EPMC7656267 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature