PMID- 20625116
OWN - NLM
STAT- MEDLINE
DCOM- 20100928
LR  - 20220812
IS  - 1527-7755 (Electronic)
IS  - 0732-183X (Linking)
VI  - 28
IP  - 23
DP  - 2010 Aug 10
TI  - Prognostic impact of isocitrate dehydrogenase enzyme isoforms 1 and 2 mutations 
      in acute myeloid leukemia: a study by the Acute Leukemia French Association 
      group.
PG  - 3717-23
LID - 10.1200/JCO.2010.28.2285 [doi]
AB  - PURPOSE: Recently, whole-genome sequencing in acute myeloid leukemia (AML) 
      identified recurrent isocitrate dehydrogenase enzyme isoform (IDH1) mutations 
      (IDH1m), previously reported to be involved in gliomas as well as IDH2 mutations 
      (IDH2m). The prognosis of both IDH1m and IDH2m in AML remains unclear. PATIENTS 
      AND METHODS: The prevalence and the prognostic impact of R132 IDH1 and R172 IDH2 
      mutations were evaluated in a cohort of 520 adults with AML homogeneously treated 
      in the French Acute Leukemia French Association (ALFA) -9801 and -9802 trials. 
      RESULTS: The prevalence of IDH1m and IDH2m was 9.6% and 3.0%, respectively, 
      mostly associated with normal cytogenetics (CN). In patients with CN-AML, IDH1m 
      were associated with NPM1m (P = .008), but exclusive of CEBPAm (P = .03). In 
      contrary, no other mutations were detected in IDH2m patients. In CN-AML patients, 
      IDH1m were found in 19% of favorable genotype ([NPM1m or CEBPAm] without 
      fms-related tyrosine kinase 3 [FLT3] internal tandem duplication [ITD]) and were 
      associated with a higher risk of relapse (RR) and a shorter overall survival 
      (OS). Favorable genotype in CN-AML could thus be defined by the association of 
      NPM1m or CEBPAm with neither FLT3-ITD nor IDH1m. In IDH2m CN-AML patients, we 
      observed a higher risk of induction failure, a higher RR and a shorter OS. In 
      multivariate analysis, age, WBC count, the four-gene favorable genotype and IDH2m 
      were independently associated with a higher RR and a shorter OS. CONCLUSION: 
      Contrarily to what is reported in gliomas, IDH1m and IDH2m in AML are associated 
      with a poor prognosis. Screening of IDH1m could help to identify high-risk 
      patients within the subset of CN-AML with a favorable genotype.
FAU - Boissel, Nicolas
AU  - Boissel N
AD  - University of Paris 7, Paris, France.
FAU - Nibourel, Olivier
AU  - Nibourel O
FAU - Renneville, Aline
AU  - Renneville A
FAU - Gardin, Claude
AU  - Gardin C
FAU - Reman, Oumedaly
AU  - Reman O
FAU - Contentin, Nathalie
AU  - Contentin N
FAU - Bordessoule, Dominique
AU  - Bordessoule D
FAU - Pautas, Cecile
AU  - Pautas C
FAU - de Revel, Thierry
AU  - de Revel T
FAU - Quesnel, Bruno
AU  - Quesnel B
FAU - Huchette, Pascal
AU  - Huchette P
FAU - Philippe, Nathalie
AU  - Philippe N
FAU - Geffroy, Sandrine
AU  - Geffroy S
FAU - Terre, Christine
AU  - Terre C
FAU - Thomas, Xavier
AU  - Thomas X
FAU - Castaigne, Sylvie
AU  - Castaigne S
FAU - Dombret, Herve
AU  - Dombret H
FAU - Preudhomme, Claude
AU  - Preudhomme C
LA  - eng
SI  - ClinicalTrials.gov/NCT00880243
SI  - ClinicalTrials.gov/NCT00931138
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100712
PL  - United States
TA  - J Clin Oncol
JT  - Journal of clinical oncology : official journal of the American Society of 
      Clinical Oncology
JID - 8309333
RN  - 0 (Protein Isoforms)
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)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Humans
MH  - Isocitrate Dehydrogenase/*genetics
MH  - Leukemia, Myeloid, Acute/*genetics
MH  - Middle Aged
MH  - Mutation
MH  - Prevalence
MH  - Prognosis
MH  - Protein Isoforms/genetics
MH  - Randomized Controlled Trials as Topic
MH  - Retrospective Studies
MH  - Young Adult
EDAT- 2010/07/14 06:00
MHDA- 2010/09/30 06:00
CRDT- 2010/07/14 06:00
PHST- 2010/07/14 06:00 [entrez]
PHST- 2010/07/14 06:00 [pubmed]
PHST- 2010/09/30 06:00 [medline]
AID - JCO.2010.28.2285 [pii]
AID - 10.1200/JCO.2010.28.2285 [doi]
PST - ppublish
SO  - J Clin Oncol. 2010 Aug 10;28(23):3717-23. doi: 10.1200/JCO.2010.28.2285. Epub 
      2010 Jul 12.