MicroRNA-486-5p is an erythroid oncomiR of the myeloid leukemias of down syndrome

Lital Shaham, Elena Vendramini, Yubin Ge, Yaron Goren, Yehudit Birger, Marloes R. Tijssen, Maureen McNulty, Ifat Geron, Omer Schwartzman, Liat Goldberg, Stella T. Chou, Holly Pitman, Mitchell J. Weiss, Shulamit Michaeli, Benjamin Sredni, Berthold Göttgens, John D. Crispino, Jeffrey W. Taub*, Shai Izraeli

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Children with Down syndrome (DS) are at increased risk for acute myeloid leukemias (ML-DS) characterized bymixedmegakaryocytic and erythroid phenotype and by acquired mutations in the GATA1 gene resulting in a short GATA1s isoform. The chromosome 21 microRNA (miR)-125b cluster has been previously shown to cooperate with GATA1s in transformation of fetal hematopoietic progenitors. In this study, we report that the expression of miR-486-5p is increased in ML-DS compared with non-DS acute megakaryocytic leukemias (AMKLs). miR-486-5p is regulated by GATA1 and GATA1s that bind to the promoter of its host gene ANK1. miR-486-5p is highly expressed in mouse erythroid precursors and knockdown (KD) inML-DS cells reduced their erythroid phenotype. Ectopic expression and KD of miR-486-5p in primary fetal liver hematopoietic progenitors demonstrated that miR-486-5pcooperateswithGata1s to enhance their self renewal.Consistent with its activation of AKT, overexpression and KD experiments showed its importance for growth and survival of human leukemic cells. Thus, miR-486-5p cooperates withGATA1s in supporting the growth and survival, and the aberrant erythroid phenotype of the megakaryocytic leukemias of DS.

Original languageEnglish (US)
Pages (from-to)1292-1301
Number of pages10
JournalBlood
Volume125
Issue number8
DOIs
StatePublished - Feb 19 2015

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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