MicroRNA-29a induces aberrant self-renewal capacity in hematopoietic progenitors, biased myeloid development, and acute myeloid leukemia Journal Article
| Authors: | Han, Y. C.; Park, C. Y.; Bhagat, G.; Zhang, J.; Wang, Y.; Fan, J. B.; Liu, M.; Zou, Y.; Weissman, I. L.; Gu, H. |
| Article Title: | MicroRNA-29a induces aberrant self-renewal capacity in hematopoietic progenitors, biased myeloid development, and acute myeloid leukemia |
| Abstract: | The function of microRNAs (miRNAs) in hematopoietic stem cells (HSCs), committed progenitors, and leukemia stem cells (LSCs) is poorly understood. We show that miR-29a is highly expressed in HSC and down-regulated in hematopoietic progenitors. Ectopic expression of miR-29a in mouse HSC/progenitors results in acquisition of self-renewal capacity by myeloid progenitors, biased myeloid differentiation, and the development of a myeloproliferative disorder that progresses to acute myeloid leukemia (AML). miR-29a promotes progenitor proliferation by expediting G1 to S/G2 cell cycle transitions. miR-29a is overexpressed in human AML and, like human LSC, miR-29a-expressing myeloid progenitors serially transplant AML. Our data indicate that miR-29a regulates early hematopoiesis and suggest that miR-29a initiates AML by converting myeloid progenitors into self-renewing LSC. © 2010 Han et al. |
| Keywords: | controlled study; protein expression; myeloproliferative disorders; unclassified drug; acute granulocytic leukemia; myeloproliferative disorder; leukemia, myeloid, acute; nonhuman; flow cytometry; protein function; cell proliferation; mouse; animals; mice; animal tissue; cell cycle; cell division; gene overexpression; microrna; animal experiment; animal model; cell renewal; cell differentiation; gene expression regulation; blood sampling; leukemogenesis; hematopoietic stem cells; stem cells; hematopoiesis; down regulation; bone marrow cell; hematopoietic stem cell; micrornas; cell cycle regulation; myeloid cells; microrna 29a; phase transition |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 207 |
| Issue: | 3 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2010-03-15 |
| Start Page: | 475 |
| End Page: | 489 |
| Language: | English |
| ACCESSION: | 64 |
| DOI: | 10.1084/jem.20090831 |
| PROVIDER: | scopus |
| PMCID: | PMC2839143 |
| PUBMED: | 20212066 |
| DOI/URL: | |
| Notes: | --- - J. Exp. Med. - "Cited By (since 1996): 46 Export Date: 13 July 2012 Source: Scopus CODEN: JEMEA PubMed ID: 20212066 Language of Original Document: English Chemicals/CAS: MIRN29 microRNA, human; MicroRNAs" - "Source: Scopus" |
