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miR-9 is a tumor suppressor in pediatric AML with t(8;21)

S. Emmrich, JE. Katsman-Kuipers, K. Henke, ME. Khatib, R. Jammal, F. Engeland, F. Dasci, CM. Zwaan, ML. den Boer, L. Verboon, J. Stary, A. Baruchel, V. de Haas, AA. Danen-van Oorschot, M. Fornerod, R. Pieters, D. Reinhardt, JH. Klusmann, MM. van...

. 2014 ; 28 (5) : 1022-32.

Language English Country England, Great Britain

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc14074475
E-resources Online Full text

NLK ProQuest Central from 2000-01-01 to 1 year ago
Open Access Digital Library from 1997-01-01
Medline Complete (EBSCOhost) from 1997-01-01 to 2015-11-30
Nursing & Allied Health Database (ProQuest) from 2000-01-01 to 1 year ago
Health & Medicine (ProQuest) from 2000-01-01 to 1 year ago
Public Health Database (ProQuest) from 2000-01-01 to 1 year ago

Links

PubMed 24270738
DOI 10.1038/leu.2013.357
Knihovny.cz E-resources

MicroRNAs (miRNAs) play a pivotal role in the regulation of hematopoiesis and development of leukemia. Great interest emerged in modulating miRNA expression for therapeutic purposes. In order to identify miRNAs, which specifically suppress leukemic growth of acute myeloid leukemia (AML) with t(8;21), inv(16) or mixed lineage leukemia (MLL) rearrangement by inducing differentiation, we conducted a miRNA expression profiling in a cohort of 90 cytogenetically characterized, de novo pediatric AML cases. Four miRNAs, specifically downregulated in MLL-rearranged, t(8;21) or inv(16) AMLs, were characterized by their tumor-suppressive properties in cell lines representing those respective cytogenetic groups. Among those, forced expression of miR-9 reduced leukemic growth and induced monocytic differentiation of t(8;21) AML cell lines in vitro and in vivo. The tumor-suppressive functions of miR-9 were specifically restricted to AML cell lines and primary leukemic blasts with t(8;21). On the other hand, these functions were not evident in AML blasts from patients with MLL rearrangements. We showed that miR-9 exerts its effects through the cooperation with let-7 to repress the oncogenic LIN28B/HMGA2 axis. Thus, miR-9 is a tumor suppressor-miR which acts in a stringent cell context-dependent manner.

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