PMID- 21130701
OWN - NLM
STAT- MEDLINE
DCOM- 20110106
LR  - 20220812
IS  - 1878-3686 (Electronic)
IS  - 1535-6108 (Print)
IS  - 1535-6108 (Linking)
VI  - 18
IP  - 6
DP  - 2010 Dec 14
TI  - Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt 
      TET2 function, and impair hematopoietic differentiation.
PG  - 553-67
LID - 10.1016/j.ccr.2010.11.015 [doi]
AB  - Cancer-associated IDH mutations are characterized by neomorphic enzyme activity 
      and resultant 2-hydroxyglutarate (2HG) production. Mutational and epigenetic 
      profiling of a large acute myeloid leukemia (AML) patient cohort revealed that 
      IDH1/2-mutant AMLs display global DNA hypermethylation and a specific 
      hypermethylation signature. Furthermore, expression of 2HG-producing IDH alleles 
      in cells induced global DNA hypermethylation. In the AML cohort, IDH1/2 mutations 
      were mutually exclusive with mutations in the alpha-ketoglutarate-dependent enzyme 
      TET2, and TET2 loss-of-function mutations were associated with similar epigenetic 
      defects as IDH1/2 mutants. Consistent with these genetic and epigenetic data, 
      expression of IDH mutants impaired TET2 catalytic function in cells. Finally, 
      either expression of mutant IDH1/2 or Tet2 depletion impaired hematopoietic 
      differentiation and increased stem/progenitor cell marker expression, suggesting 
      a shared proleukemogenic effect.
CI  - Copyright (c) 2010 Elsevier Inc. All rights reserved.
FAU - Figueroa, Maria E
AU  - Figueroa ME
AD  - Weill Cornell Medical College, New York, NY 10065, USA.
FAU - Abdel-Wahab, Omar
AU  - Abdel-Wahab O
FAU - Lu, Chao
AU  - Lu C
FAU - Ward, Patrick S
AU  - Ward PS
FAU - Patel, Jay
AU  - Patel J
FAU - Shih, Alan
AU  - Shih A
FAU - Li, Yushan
AU  - Li Y
FAU - Bhagwat, Neha
AU  - Bhagwat N
FAU - Vasanthakumar, Aparna
AU  - Vasanthakumar A
FAU - Fernandez, Hugo F
AU  - Fernandez HF
FAU - Tallman, Martin S
AU  - Tallman MS
FAU - Sun, Zhuoxin
AU  - Sun Z
FAU - Wolniak, Kristy
AU  - Wolniak K
FAU - Peeters, Justine K
AU  - Peeters JK
FAU - Liu, Wei
AU  - Liu W
FAU - Choe, Sung E
AU  - Choe SE
FAU - Fantin, Valeria R
AU  - Fantin VR
FAU - Paietta, Elisabeth
AU  - Paietta E
FAU - Lowenberg, Bob
AU  - Lowenberg B
FAU - Licht, Jonathan D
AU  - Licht JD
FAU - Godley, Lucy A
AU  - Godley LA
FAU - Delwel, Ruud
AU  - Delwel R
FAU - Valk, Peter J M
AU  - Valk PJ
FAU - Thompson, Craig B
AU  - Thompson CB
FAU - Levine, Ross L
AU  - Levine RL
FAU - Melnick, Ari
AU  - Melnick A
LA  - eng
GR  - R01 CA173636/CA/NCI NIH HHS/United States
GR  - U54 CA143798/CA/NCI NIH HHS/United States
GR  - CA 114737/CA/NCI NIH HHS/United States
GR  - U10 CA021115/CA/NCI NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - U54CA143798-01/CA/NCI NIH HHS/United States
GR  - R01 HL082950/HL/NHLBI NIH HHS/United States
GR  - R01 CA105463/CA/NCI NIH HHS/United States
GR  - CA21115/CA/NCI NIH HHS/United States
GR  - U24 CA114737/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20101209
PL  - United States
TA  - Cancer Cell
JT  - Cancer cell
JID - 101130617
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (GATA1 Transcription Factor)
RN  - 0 (GATA1 protein, human)
RN  - 0 (MDS1 and EVI1 Complex Locus Protein)
RN  - 0 (MECOM protein, human)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Transcription Factors)
RN  - 6R795CQT4H (5-Methylcytosine)
RN  - EC 1.1.1.41 (IDH2 protein, human)
RN  - EC 1.1.1.41 (Isocitrate Dehydrogenase)
RN  - EC 1.1.1.42. (IDH1 protein, human)
RN  - EC 1.13.11.- (Dioxygenases)
RN  - EC 1.13.11.- (TET2 protein, human)
SB  - IM
MH  - 5-Methylcytosine/metabolism
MH  - Cell Differentiation
MH  - *DNA Methylation
MH  - DNA-Binding Proteins/genetics/metabolism/*physiology
MH  - Dioxygenases
MH  - GATA1 Transcription Factor/metabolism
MH  - Gene Regulatory Networks
MH  - Humans
MH  - Hydroxylation
MH  - Isocitrate Dehydrogenase/*genetics
MH  - Leukemia, Myeloid, Acute/*genetics
MH  - MDS1 and EVI1 Complex Locus Protein
MH  - *Mutation
MH  - Myeloid Cells/*cytology
MH  - Phenotype
MH  - Proto-Oncogene Proteins/genetics/*physiology
MH  - Proto-Oncogenes
MH  - Transcription Factors/metabolism
PMC - PMC4105845
MID - NIHMS253994
EDAT- 2010/12/07 06:00
MHDA- 2011/01/07 06:00
PMCR- 2014/07/22
CRDT- 2010/12/07 06:00
PHST- 2010/09/26 00:00 [received]
PHST- 2010/11/06 00:00 [revised]
PHST- 2010/11/11 00:00 [accepted]
PHST- 2010/12/07 06:00 [entrez]
PHST- 2010/12/07 06:00 [pubmed]
PHST- 2011/01/07 06:00 [medline]
PHST- 2014/07/22 00:00 [pmc-release]
AID - S1535-6108(10)00483-6 [pii]
AID - 10.1016/j.ccr.2010.11.015 [doi]
PST - ppublish
SO  - Cancer Cell. 2010 Dec 14;18(6):553-67. doi: 10.1016/j.ccr.2010.11.015. Epub 2010 
      Dec 9.