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

S Emmrich, J E Katsman-Kuipers, K Henke, M E Khatib, R Jammal, F Engeland, F Dasci, C M Zwaan, M L den Boer, L Verboon, J Stary, A Baruchel, V de Haas, A A Danen-van Oorschot, M Fornerod, R Pieters, D Reinhardt, J H Klusmann, M M van den Heuvel-Eibrink

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1022-32
Number of pages11
Issue number5
Publication statusPublished - May 2014
Externally publishedYes


  • Animals
  • Cell Division
  • Child
  • Chromosomes, Human, Pair 21
  • Chromosomes, Human, Pair 8
  • Female
  • Flow Cytometry
  • Genes, Tumor Suppressor
  • Heterografts
  • Humans
  • Leukemia, Myeloid, Acute/genetics
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs/genetics
  • Translocation, Genetic


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