PMID- 20805365
OWN - NLM
STAT- MEDLINE
DCOM- 20110208
LR  - 20211203
IS  - 1528-0020 (Electronic)
IS  - 0006-4971 (Linking)
VI  - 116
IP  - 25
DP  - 2010 Dec 16
TI  - IDH1 mutations are detected in 6.6% of 1414 AML patients and are associated with 
      intermediate risk karyotype and unfavorable prognosis in adults younger than 60 
      years and unmutated NPM1 status.
PG  - 5486-96
LID - 10.1182/blood-2010-02-267955 [doi]
AB  - Mutations in the IDH1 gene at position R132 coding for the enzyme cytosolic 
      isocitrate dehydrogenase are known in glioma and have recently been detected also 
      in acute myeloid leukemia (AML). These mutations result in an accumulation of 
      alpha-ketoglutarate to R (2)-2-hydroxyglutarate (2HG). To further clarify the role of 
      this mutation in AML, we have analyzed IDH1R132 in 1414 AML patients. We detected 
      IDH1R132 mutations in 93 of 1414 patients (6.6%) with a clear prevalence in 
      intermediate risk karyotype group (10.4%, P < .001). Although IDH1R132 mutations 
      can incidentally occur together with all other molecular markers, there were 
      strong associations with NPM1 mutations (14.2% vs 5.4% in NPM1wt, P < .001) and 
      MLL-PTD (18.2% vs 7.0% in MLLwt, P = .020). IDH1-mutated cases more often had AML 
      without maturation/French-American-British M1 (P < .001), an immature 
      immunophenotype, and female sex (8.7% vs 4.7% in male, P = .003) compared with 
      IDH1wt cases. Prognosis was adversely affected by IDH1 mutations with trend for 
      shorter overall survival (P = .110), a shorter event-free survival (P < .003) and 
      a higher cumulative risk for relapse (P = .001). IDH1 mutations were of 
      independent prognostic relevance for event-free survival (P = .039) especially in 
      the age group < 60 years (P = .028). In conclusion, these data show that IDH1R132 
      may significantly add information regarding characterization and prognostication 
      in AML.
FAU - Schnittger, Susanne
AU  - Schnittger S
AD  - Munich Leukemia Laboratory, Munich, Germany. susanne.schnittger@mll.com
FAU - Haferlach, Claudia
AU  - Haferlach C
FAU - Ulke, Madlen
AU  - Ulke M
FAU - Alpermann, Tamara
AU  - Alpermann T
FAU - Kern, Wolfgang
AU  - Kern W
FAU - Haferlach, Torsten
AU  - Haferlach T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
DEP - 20100830
PL  - United States
TA  - Blood
JT  - Blood
JID - 7603509
RN  - 0 (DNA, Neoplasm)
RN  - 0 (NPM1 protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 117896-08-9 (Nucleophosmin)
RN  - EC 1.1.1.41 (Isocitrate Dehydrogenase)
RN  - EC 1.1.1.42. (IDH1 protein, human)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - DNA, Neoplasm/genetics
MH  - Female
MH  - Genotype
MH  - Humans
MH  - Immunophenotyping
MH  - Isocitrate Dehydrogenase/*genetics
MH  - Karyotyping
MH  - Leukemia, Myeloid, Acute/classification/*genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Mutation/*genetics
MH  - Nuclear Proteins/*genetics
MH  - Nucleophosmin
MH  - Polymerase Chain Reaction
MH  - Prognosis
MH  - Risk Factors
MH  - Survival Rate
MH  - Young Adult
EDAT- 2010/09/02 06:00
MHDA- 2011/02/09 06:00
CRDT- 2010/09/01 06:00
PHST- 2010/09/01 06:00 [entrez]
PHST- 2010/09/02 06:00 [pubmed]
PHST- 2011/02/09 06:00 [medline]
AID - S0006-4971(20)60343-3 [pii]
AID - 10.1182/blood-2010-02-267955 [doi]
PST - ppublish
SO  - Blood. 2010 Dec 16;116(25):5486-96. doi: 10.1182/blood-2010-02-267955. Epub 2010 
      Aug 30.