CaltechAUTHORS
Published August 28, 2014 | Version Published
Journal Article Open

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

Creators

  • 1. ROR icon California Institute of Technology
  • 2. ROR icon Stanford University
  • 3. ROR icon University of California, San Diego
  • 4. ROR icon Case Western Reserve University

Abstract

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.

Additional Information

© 2014 American Society of Hematology. Submitted January 31, 2014; accepted June 21, 2014. Prepublished online as Blood First Edition paper, July 8, 2014. The authors thank all members of the Baltimore laboratory and funding sources. This work was supported by National Institutes of Health (National Cancer Institute) 1F32 CA139883-01A1 and (National Heart, Lung, and Blood Institute) K99HL118754 (A.Y.-L.S.), the Paul and Daisy Soros Fellowship and the National Science Foundation Graduate Research Fellowship (A.A.C.), and National Institutes of Health (National Institute of Allergy and Infectious Diseases) 1RO1AI079243 and 1R01AI093531 (D.B.). The authors declare no competing financial interests.

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Published - blood-2014-02-553842.full.pdf

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Additional details

Identifiers

PMCID
PMC4148772
Eprint ID
47165
Resolver ID
CaltechAUTHORS:20140714-102030576

Funding

NIH
1F32 CA139883-01A1
NIH
K99HL118754
Paul and Daisy Soros Fellowship
NSF Graduate Research Fellowship
NIH
1RO1AI079243-01
NIH
1R01AI093531

Dates

Created
2014-07-14
Created from EPrint's datestamp field
Updated
2021-11-10
Created from EPrint's last_modified field