MIR142Loss-of-Function Mutations Promote Leukemogenesis through Derepression of ASH1LResulting in Increased HOXGene Expression

Mutations of MIR142have been identified in approximately 2% of de novoAML and in 20% of diffuse large B cell lymphoma (DLBCL). In AML, all of the mutations in MIR142localize to the seed sequence of miRNA-142-3p, which is crucial in determining its target specificity. Previously, we showed that these mutations disrupt both miRNA-142-3p and miRNA-142-5p function, suggesting that loss of MIR142plays a role in leukemic transformation (Yao et al, ASH abstract 1254, 2015). To test this hypothesis, we first characterized hematopoiesis in Mir142-/-mice. We previously reported that loss of Mir142results in an expansion of myeloid progenitors with impaired erythropoiesis and lymphopoiesis (Yao, ASH abstract 1254, 2015). We now extend these analyses to investigate how loss of Mir142promotes leukemic transformation.