Prognostic significance of alterations in IDH enzyme isoforms in patients with AML treated with high-dose cytarabine and idarubicin.
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.
Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. fravandi@mdanderson.org
Farhad
F
Ravandi
Keyur
K
Patel
Rajyalakshmi
R
Luthra
Stefan
S
Faderl
Marina
M
Konopleva
Tapan
T
Kadia
Mark
M
Brandt
Sherry
S
Pierce
Steven
S
Kornblau
Michael
M
Andreeff
Xuemei
X
Wang
Guillermo
G
Garcia-Manero
Jorge
J
Cortes
Hagop
H
Kantarjian
D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage; D006801:Humans; D015255:Idarubicin / Q000008:administration & dosage; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D009154:Mutation; D000090243:Nucleophosmin; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis
C000716967:NPM1 protein, human; D003561:Cytarabine; D000090243:Nucleophosmin; C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human; D015255:Idarubicin