microRNA-29a induces aberrant self-renewal capacity in hematopoietic progenitors, biased myeloid development, and acute myeloid leukemia

J Exp Med. 2010 Mar 15;207(3):475-89. doi: 10.1084/jem.20090831. Epub 2010 Mar 8.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle
  • Cell Division
  • Gene Expression Regulation
  • Hematopoiesis
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / physiology
  • Humans
  • Leukemia, Myeloid, Acute / genetics*
  • Mice
  • MicroRNAs / genetics
  • MicroRNAs / physiology*
  • Myeloid Cells / physiology*
  • Myeloproliferative Disorders / genetics
  • Stem Cells / cytology
  • Stem Cells / physiology

Substances

  • MIRN29 microRNA, human
  • MicroRNAs