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Presence of isocitrate dehydrogenase mutations may predict clinical response to hypomethylating agents in patients with acute myeloid leukemia
Author(s) -
Emadi Ashkan,
Faramand Rawan,
CarterCooper Brandon,
Tolu Seda,
Ford Laurie A.,
Lapidus Rena G.,
Wetzler Meir,
Wang Eunice S.,
Etemadi Arash,
Griffiths Elizabeth A.
Publication year - 2015
Publication title -
american journal of hematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.456
H-Index - 105
eISSN - 1096-8652
pISSN - 0361-8609
DOI - 10.1002/ajh.23965
Subject(s) - idh2 , isocitrate dehydrogenase , decitabine , azacitidine , idh1 , myeloid leukemia , medicine , oncology , mutation , cancer research , hypomethylating agent , gastroenterology , biology , dna methylation , gene , genetics , biochemistry , gene expression , enzyme
Mutations in IDH1 and IDH2 occur in 15–20% of AML cases, resulting in the production of 2‐hydroxyglutarate, which promotes aberrant hypermethylation of DNA in leukemic cells. Although these mutations have been shown to have prognostic implications for patients with AML, optimal treatment strategies have yet to be defined. We retrospectively identified forty‐two patients with AML treated with DNA methyltransferase inhibitors (DNMTIs) decitabine ( n = 36) or azacitidine ( n = 6) and performed analysis of stored samples for the presence of IDH1 and IDH2 mutations. Of the forty‐two samples analyzed, seven (16.7%) had IDH mutations. Thirteen patients (31%) achieved remission [(complete remission (CR)/complete remission with incomplete count recovery (CRi)/partial response (PR)] after treatment with a DNMTI, five of seven (71.4%) with IDH mutations and eight of thirty‐five (22.9%) without IDH mutations ( P = 0.01). When adjusted for age at diagnosis, sex, bone marrow blast percentage and cytogenetic, the odds of achieving response after administration of a DNMTI among patients with an IDH mutation was 14.2 when compared to patients without an IDH mutation (95%CI: 1.3–150.4). IDH1 and IDH2 mutations may predict a favorable response to DNMTI in patients with AML. Am. J. Hematol. 90:E77–E79, 2015. © 2015 Wiley Periodicals, Inc.