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

So, Alex Yick-Lun and Sookram, Reeshelle and Chaudhuri, Aadel A. and Minisandram, Aarathi and Cheng, David and Xie, Catherine and Lim, Ee Lyn and Garcia Flores, Yvette and Jiang, Shuai and Kim, Jocelyn T. and Keown, Christopher and Ramakrishnan, Parameswaran and Baltimore, David (2014) Dual mechanisms by which MiR-125b represses IRF4 to induce myeloid and B cell leukemias. Blood, 124 (9). pp. 1502-1512. ISSN 0006-4971. PMCID PMC4148772. http://resolver.caltech.edu/CaltechAUTHORS:20140714-102030576

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://bloodjournal.hematologylibrary.org/content/early/2014/07/08/blood-2014-02-553842.longPublisherArticle
http://dx.doi.org/10.1182/blood-2014-02-553842DOIArticle
http://www.bloodjournal.org/content/124/9/1502PublisherArticle
ORCID:
AuthorORCID
Kim, Jocelyn T.0000-0001-8723-8190
Ramakrishnan, Parameswaran0000-0002-1314-827X
Baltimore, David0000-0001-8723-8190
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.
Funders:
Funding AgencyGrant Number
NIH1F32 CA139883-01A1
NIHK99HL118754
Paul and Daisy Soros FellowshipUNSPECIFIED
NSF Graduate Research FellowshipUNSPECIFIED
NIH1RO1AI079243-01
NIH1R01AI093531
Subject Keywords:MiR-125b induces tumorigenesis in myeloid cells by repressing the expression of IRF4 at the mRNA and protein level. MiR-125b promotes oncogenesis in B cells that involves selection of cells that acquire genetic deletion of the gene encoding IRF4.
PubMed Central ID:PMC4148772
Record Number:CaltechAUTHORS:20140714-102030576
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20140714-102030576
Official Citation: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 Blood Aug 2014, 124(9)1502-1512;DOI: 10.1182/blood-2014-02-553842
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:47165
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:14 Jul 2014 19:36
Last Modified:08 Nov 2017 00:29

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