Blood Journal
Leading the way in experimental and clinical research in hematology

MicroRNA 29b functions in acute myeloid leukemia

  1. Ramiro Garzon1,
  2. Catherine E. A. Heaphy1,
  3. Violaine Havelange2,
  4. Muller Fabbri2,
  5. Stefano Volinia2,
  6. Twee Tsao3,
  7. Nicola Zanesi2,
  8. Steven M. Kornblau3,
  9. Guido Marcucci1,
  10. George A. Calin4,
  11. Michael Andreeff3, and
  12. Carlo M. Croce2
  1. 1Division of Hematology and Oncology, Department of Medicine and
  2. 2Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus; and
  3. 3Section of Molecular Hematology and Therapy, Department of Blood and Bone Marrow Transplantation and
  4. 4Department of Experimental Therapeutics, University of Texas M. D. Anderson Cancer Center, Houston

Abstract

MicroRNAs (miRNAs) are associated with cytogenetics and molecular subtypes of acute myelogeneous leukemia (AML), but their impact on AML pathogenesis is poorly understood. We have previously shown that miR-29b expression is deregulated in primary AML blasts. In this work, we investigated the functional role of miR-29b in leukemogenesis. Restoration of miR-29b in AML cell lines and primary samples induces apoptosis and dramatically reduces tumorigenicity in a xenograft leukemia model. Transcriptome analysis after ectopic transfection of synthetic miR-29b into leukemia cells indicates that miR-29b target apoptosis, cell cycle, and proliferation pathways. A significant enrichment for apoptosis genes, including MCL-1, was found among the mRNAs inversely correlated with miR-29b expression in 45 primary AML samples. Together, the data support a tumor suppressor role for miR-29 and provide a rationale for the use of synthetic miR-29b oligonucleotides as a novel strategy to improve treatment response in AML.

  • Submitted March 18, 2009.
  • Accepted September 28, 2009.
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