TY - JOUR
T1 - MicroRNA 29b functions in acute myeloid leukemia
AU - Garzon, Ramiro
AU - Heaphy, Catherine E.A.
AU - Havelange, Violaine
AU - Fabbri, Muller
AU - Volinia, Stefano
AU - Tsao, Twee
AU - Zanesi, Nicola
AU - Kornblau, Steven M.
AU - Marcucci, Guido
AU - Calin, George A.
AU - Andreeff, Michael
AU - Croce, Carlo M.
PY - 2009/12/17
Y1 - 2009/12/17
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=73949118737&partnerID=8YFLogxK
U2 - 10.1182/blood-2009-03-211938
DO - 10.1182/blood-2009-03-211938
M3 - Article
C2 - 19850741
AN - SCOPUS:73949118737
SN - 0006-4971
VL - 114
SP - 5331
EP - 5341
JO - Blood
JF - Blood
IS - 26
ER -