MicroRNA 29b functions in acute myeloid leukemia

Ramiro Garzon, Catherine E.A. Heaphy, Violaine Havelange, Muller Fabbri, Stefano Volinia, Twee Tsao, Nicola Zanesi, Steven M. Kornblau, Guido Marcucci, George A. Calin, Michael Andreeff, Carlo M. Croce

Research output: Contribution to journalArticlepeer-review

371 Scopus citations

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.

Original languageEnglish
Pages (from-to)5331-5341
Number of pages11
JournalBlood
Volume114
Issue number26
DOIs
StatePublished - 17 Dec 2009
Externally publishedYes

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