Dual Mechanisms by which MiR-125b Represses IRF4 to Induce Myeloid and B cell Leukemias. Mus musculus

The oncomir microRNA-125b (miR-125b) is up-regulated in a variety of human neoplastic blood disorders and constitutive up-regulation of miR-125b in mice can promote myeloid and B cell leukemia. We found that miR-125b promotes myeloid and B cell neoplasm by inducing tumorigenesis in hematopoietic progenitor cells. Our study demonstrates that miR-125b induces myeloid leukemia by enhancing myeloid progenitor output from stem cells as well as inducing immortality, self-renewal, and tumorigenesis in myeloid progenitors. Through functional and genetic analyses, we demonstrated that miR-125b induces myeloid and B cell leukemia by inhibiting IRF4 but through distinct mechanisms; it induces myeloid leukemia through repressing IRF4 at the mRNA level without altering the genomic DNA and induces B cell leukemia via genetic deletion of the gene encoding IRF4. Overall design: The cancer myeloid (Cd11b+ sorted) and B cells (CD19+ sorted) were harvested from mice that over-express miR-125b. The genomic DNA was extracted from these cells. A total of 4 cancer samples (Two myeloid cancer samples and two B cell cancer samples) were analyzed. As control, genomic DNA from cells harvested from healthy C57bl/6 mice were harvested.