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Cancer. 2012 May 15;118(10):2665-73. doi: 10.1002/cncr.26580. Epub 2011 Oct 21.

Prognostic significance of alterations in IDH enzyme isoforms in patients with AML treated with high-dose cytarabine and idarubicin.

Author information

1
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. fravandi@mdanderson.org

Abstract

BACKGROUND:

IDH1 and IDH2 gene mutations are novel, recurring molecular aberrations among patients with normal karyotype acute myeloid leukemia (AML).

METHODS:

Among 358 patients with AML treated on 4 protocols using high-dose ara-C plus idarubicin induction, pretreatment samples were available for 170 (median age 53 years, [range, 17-73]; 96% ≤65) and were evaluated for IDH1R132, IDH2R172, and IDH2R140 mutations or the codon 105 single nucleotide polymorphism (SNP) in IDH1.

RESULTS:

IDH1 and IDH2 mutations were present in 12 (7%) and 24 (14%) of patients, and IDH1 G105 SNP in 24 (14%). Overall, 52 (30%) patients had IDH gene alterations. There was no association with complete response (CR), remission duration, overall survival, and event-free survival and any of the IDH alterations, and no association with a higher CR rate or survival with the 4 regimens for the 52 patients with aberrant IDH. Among the patients with diploid karyotype and NPM1(mut) FLT3(WT) genotype, those with IDH1 or IDH2 mutations had an inferior outcome.

CONCLUSIONS:

IDH aberrations and IDH1 codon 105 SNP occur in about 30% of younger patients with AML, mostly with diploid karyotype. Using high-dose ara-C-based induction regimens, we did not detect an association with outcome for any of the aberrations.

PMID:
22020636
PMCID:
PMC4060157
DOI:
10.1002/cncr.26580
[Indexed for MEDLINE]
Free PMC Article

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