Journal
BLOOD
Volume 124, Issue 9, Pages 1502-1512Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2014-02-553842
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Funding
- National Institutes of Health (National Cancer Institute) [1F32 CA139883-01A1, K99HL118754]
- Paul and Daisy Soros Fellowship
- National Science Foundation
- National Institutes of Health (National Institute of Allergy and Infectious Diseases) [1RO1AI079243, 1R01AI093531]
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The oncomir microRNA-125b (miR-125b) is upregulated in a variety of human neoplastic blood disorders and constitutive upregulation 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 interferon regulatory factor 4 (IRF4) but through distinct mechanisms; it induces myeloid leukemia through repressing IRF4 at the messenger RNA (mRNA) level without altering the genomic DNA and induces B-cell leukemia via genetic deletion of the gene encoding IRF4.
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