PMID- 25533034
OWN - NLM
STAT- MEDLINE
DCOM- 20150424
LR  - 20220129
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Print)
IS  - 0006-4971 (Linking)
VI  - 125
IP  - 8
DP  - 2015 Feb 19
TI  - MicroRNA-486-5p is an erythroid oncomiR of the myeloid leukemias of Down 
      syndrome.
PG  - 1292-301
LID - 10.1182/blood-2014-06-581892 [doi]
AB  - Children with Down syndrome (DS) are at increased risk for acute myeloid 
      leukemias (ML-DS) characterized by mixed megakaryocytic 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) 
      in ML-DS cells reduced their erythroid phenotype. Ectopic expression and KD of 
      miR-486-5p in primary fetal liver hematopoietic progenitors demonstrated that 
      miR-486-5p cooperates with Gata1s 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 with 
      GATA1s in supporting the growth and survival, and the aberrant erythroid 
      phenotype of the megakaryocytic leukemias of DS.
CI  - (c) 2015 by The American Society of Hematology.
FAU - Shaham, Lital
AU  - Shaham L
AD  - Childhood Leukemia Research Institute, Cancer Research Center, Sheba Medical 
      Center, Ramat-Gan, Israel; Department of Life Sciences, Bar-Ilan University, 
      Ramat-Gan, Israel;
FAU - Vendramini, Elena
AU  - Vendramini E
AD  - Childhood Leukemia Research Institute, Cancer Research Center, Sheba Medical 
      Center, Ramat-Gan, Israel; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 
      Israel;
FAU - Ge, Yubin
AU  - Ge Y
AD  - Department of Oncology, Molecular Therapeutics Program, Barbara Ann Karmanos 
      Cancer Institute, Wayne State University School of Medicine, Detroit, MI;
FAU - Goren, Yaron
AU  - Goren Y
AD  - Rosetta Genomics Ltd, Rehovot, Israel;
FAU - Birger, Yehudit
AU  - Birger Y
AD  - Childhood Leukemia Research Institute, Cancer Research Center, Sheba Medical 
      Center, Ramat-Gan, Israel;
FAU - Tijssen, Marloes R
AU  - Tijssen MR
AD  - Department of Haematology, Cambridge Institute for Medical Research and Wellcome 
      Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, 
      United Kingdom;
FAU - McNulty, Maureen
AU  - McNulty M
AD  - Division of Hematology/Oncology, Northwestern University, Chicago, IL;
FAU - Geron, Ifat
AU  - Geron I
AD  - Childhood Leukemia Research Institute, Cancer Research Center, Sheba Medical 
      Center, Ramat-Gan, Israel; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 
      Israel;
FAU - Schwartzman, Omer
AU  - Schwartzman O
AD  - Childhood Leukemia Research Institute, Cancer Research Center, Sheba Medical 
      Center, Ramat-Gan, Israel; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 
      Israel;
FAU - Goldberg, Liat
AU  - Goldberg L
AD  - Childhood Leukemia Research Institute, Cancer Research Center, Sheba Medical 
      Center, Ramat-Gan, Israel;
FAU - Chou, Stella T
AU  - Chou ST
AD  - Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, 
      PA;
FAU - Pitman, Holly
AU  - Pitman H
AD  - Department of Oncology, Molecular Therapeutics Program, Barbara Ann Karmanos 
      Cancer Institute, Wayne State University School of Medicine, Detroit, MI;
FAU - Weiss, Mitchell J
AU  - Weiss MJ
AD  - Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, 
      PA;
FAU - Michaeli, Shulamit
AU  - Michaeli S
AD  - Department of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel; Institute of 
      Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat-Gan, Israel; and.
FAU - Sredni, Benjamin
AU  - Sredni B
AD  - Department of Life Sciences, Bar-Ilan University, Ramat-Gan, Israel;
FAU - Gottgens, Berthold
AU  - Gottgens B
AD  - Department of Haematology, Cambridge Institute for Medical Research and Wellcome 
      Trust and MRC Cambridge Stem Cell Institute, University of Cambridge, Cambridge, 
      United Kingdom;
FAU - Crispino, John D
AU  - Crispino JD
AD  - Division of Hematology/Oncology, Northwestern University, Chicago, IL;
FAU - Taub, Jeffrey W
AU  - Taub JW
AD  - Department of Oncology, Molecular Therapeutics Program, Barbara Ann Karmanos 
      Cancer Institute, Wayne State University School of Medicine, Detroit, MI; 
      Division of Pediatric Hematology and Oncology, Children's Hospital of Michigan, 
      Detroit, MI.
FAU - Izraeli, Shai
AU  - Izraeli S
AD  - Childhood Leukemia Research Institute, Cancer Research Center, Sheba Medical 
      Center, Ramat-Gan, Israel; Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 
      Israel;
LA  - eng
GR  - U10CA098543/CA/NCI NIH HHS/United States
GR  - T32 CA009560/CA/NCI NIH HHS/United States
GR  - Biotechnology and Biological Sciences Research Council/United Kingdom
GR  - U10CA180886/CA/NCI NIH HHS/United States
GR  - CA120772/CA/NCI NIH HHS/United States
GR  - P01 HL064190/HL/NHLBI NIH HHS/United States
GR  - U10 CA098543/CA/NCI NIH HHS/United States
GR  - R01 CA120772/CA/NCI NIH HHS/United States
GR  - P01 HL110860/HL/NHLBI NIH HHS/United States
GR  - U10 CA180886/CA/NCI NIH HHS/United States
GR  - U01 HL099656/HL/NHLBI NIH HHS/United States
GR  - MC_PC_12009/MRC_/Medical Research Council/United Kingdom
GR  - R01 DK092318/DK/NIDDK NIH HHS/United States
GR  - 12765/CRUK_/Cancer Research UK/United Kingdom
GR  - Wellcome Trust/United Kingdom
GR  - U01 HL099993/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20141222
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (MIRN486 microRNA, human)
RN  - 0 (MicroRNAs)
SB  - IM
EIN - Blood. 2016 Apr 21;127(16):2042
CIN - Blood. 2015 Feb 19;125(8):1202-3. PMID: 25700423
EIN - Blood. 2016 Apr 21;127(16):2042. PMID: 31265493
MH  - Animals
MH  - Cell Differentiation/genetics
MH  - Cell Proliferation/genetics
MH  - Cell Transformation, Neoplastic/genetics
MH  - Child, Preschool
MH  - Down Syndrome/complications/*genetics/physiopathology
MH  - Erythroid Cells/metabolism
MH  - Erythropoiesis/*genetics
MH  - HEK293 Cells
MH  - Humans
MH  - K562 Cells
MH  - Leukemia, Myeloid, Acute/*genetics/pathology
MH  - Megakaryocytes/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - MicroRNAs/genetics/*physiology
MH  - Tumor Cells, Cultured
PMC - PMC4335082
EDAT- 2014/12/24 06:00
MHDA- 2015/04/25 06:00
PMCR- 2016/02/19
CRDT- 2014/12/24 06:00
PHST- 2014/12/24 06:00 [entrez]
PHST- 2014/12/24 06:00 [pubmed]
PHST- 2015/04/25 06:00 [medline]
PHST- 2016/02/19 00:00 [pmc-release]
AID - S0006-4971(20)35247-2 [pii]
AID - 2014/581892 [pii]
AID - 10.1182/blood-2014-06-581892 [doi]
PST - ppublish
SO  - Blood. 2015 Feb 19;125(8):1292-301. doi: 10.1182/blood-2014-06-581892. Epub 2014 
      Dec 22.