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

Farhad Ravandi, Keyur Patel, Rajyalakshmi Luthra, Stefan Faderl, Marina Konopleva, Tapan Kadia, Mark Brandt, Sherry Pierce, Steven Kornblau, Michael Andreeff, Xuemei Wang, Guillermo Garcia-Manero, Jorge Cortes, Hagop Kantarjian

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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;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;.

Original languageEnglish (US)
Pages (from-to)2665-2673
Number of pages9
JournalCancer
Volume118
Issue number10
DOIs
StatePublished - May 15 2012

Keywords

  • AML
  • IDH
  • SNP
  • mutations
  • outcome

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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