TY - JOUR
T1 - Prognostic significance of alterations in IDH enzyme isoforms in patients with AML treated with high-dose cytarabine and idarubicin
AU - Ravandi, Farhad
AU - Patel, Keyur
AU - Luthra, Rajyalakshmi
AU - Faderl, Stefan
AU - Konopleva, Marina
AU - Kadia, Tapan
AU - Brandt, Mark
AU - Pierce, Sherry
AU - Kornblau, Steven
AU - Andreeff, Michael
AU - Wang, Xuemei
AU - Garcia-Manero, Guillermo
AU - Cortes, Jorge
AU - Kantarjian, Hagop
PY - 2012/5/15
Y1 - 2012/5/15
N2 - 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;bsupesupbsupesup&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. Cancer 2011;.
AB - 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;bsupesupbsupesup&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. Cancer 2011;.
KW - AML
KW - IDH
KW - SNP
KW - mutations
KW - outcome
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U2 - 10.1002/cncr.26580
DO - 10.1002/cncr.26580
M3 - Article
C2 - 22020636
AN - SCOPUS:84860677744
SN - 0008-543X
VL - 118
SP - 2665
EP - 2673
JO - Cancer
JF - Cancer
IS - 10
ER -