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

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)...

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Published in:	Leukemia Vol. 28; no. 5; pp. 1022 - 1032
Main Authors:	Emmrich, S, Katsman-Kuipers, J E, Henke, K, Khatib, M E, Jammal, R, Engeland, F, Dasci, F, Zwaan, C M, den Boer, M L, Verboon, L, Stary, J, Baruchel, A, de Haas, V, Danen-van Oorschot, A A, Fornerod, M, Pieters, R, Reinhardt, D, Klusmann, J H, van den Heuvel-Eibrink, M M
Format:	Journal Article
Language:	English
Published:	London Nature Publishing Group UK 01-05-2014 Nature Publishing Group
Subjects:	631/337/384/331 631/67/581 692/699/67/1990/283/1897 692/699/67/2332 Acute myeloid leukemia Animals Bone marrow Cancer Research Care and treatment Cell Division Child Chromosomes, Human, Pair 21 Chromosomes, Human, Pair 8 Critical Care Medicine Cytogenetics Development and progression Differentiation DNA methylation Female Flow Cytometry Gene expression Genes, Tumor Suppressor Genetic aspects Health aspects Hematology Hematopoiesis Heterografts Humans Intensive Internal Medicine Leukemia Leukemia in children Leukemia, Myeloid, Acute - genetics Leukemia, Myeloid, Acute - pathology Male Medical prognosis Medicine Medicine & Public Health Mice Mice, Nude MicroRNA MicroRNAs MicroRNAs - genetics miRNA Monocytes Oncology original-article Pediatrics Therapeutic applications Translocation, Genetic Tumor cell lines Tumor suppressor genes Tumors Netherlands France United States > US Germany Paris France AML1-ETO microRNA HMGA2 miR-9 LIN28B t(8;21)
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23
ISSN:	0887-6924 1476-5551
DOI:	10.1038/leu.2013.357