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Leukemia. 2014 May;28(5):1022-32. doi: 10.1038/leu.2013.357. Epub 2013 Nov 25.

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

Author information

  • 1Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany.
  • 2Pediatric Oncology/Hematology/Biochemistry, Erasmus MC/Sophia Children's Hospital, Rotterdam, The Netherlands.
  • 3Pediatric Hematology/Oncology, Charles University and University Hospital Motol, Prague, Czech Republic.
  • 4Hematology, St. Louis Hospital, Paris, France.
  • 5Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands.

Abstract

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.

PMID:
24270738
[PubMed - indexed for MEDLINE]
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