Dual mechanisms by which miR-125b represses IRF4 to induce myeloid and B-cell leukemias

Alex Yick Lun So, Reeshelle Sookram, Aadel A. Chaudhuri, Aarathi Minisandram, David Cheng, Catherine Xie, Ee Lyn Lim, Yvette Garcia Flores, Shuai Jiang, Jocelyn Tammy Kim, Christopher Keown, Parameswaran Ramakrishnan, David Baltimore

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

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 promotemyeloid and B-cell leukemia.We found thatmiR-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 themessenger RNA (mRNA) level without altering the genomic DNA and induces B-cell leukemia via genetic deletion of the gene encoding IRF4.

Original languageEnglish
Pages (from-to)1502-1512
Number of pages11
JournalBlood
Volume124
Issue number9
DOIs
StatePublished - Aug 28 2014

Fingerprint

Dive into the research topics of 'Dual mechanisms by which miR-125b represses IRF4 to induce myeloid and B-cell leukemias'. Together they form a unique fingerprint.

Cite this