Single nucleotide polymorphisms of cytarabine metabolic genes influence clinical outcome in acute myeloid leukemia patients receiving high-dose cytarabine therapy.
Cytarabine arabinoside (Ara-C) is the most important agent for treating acute myeloid leukemia (AML). Here, we genotyped 11 single nucleotide polymorphisms (SNPs) of seven Ara-C metabolism-related genes in 39 AML patients who had received high-dose Ara-C as a single-agent treatment. Univariate analysis identified three SNPs that were significantly associated with shorter time-to-relapse (TTR): CTPS rs12144160 GG compared to AA/AG, DCTD rs9990999 AG/GG compared to AA, and SLC29A1 rs693955 CC compared to AA/AC. Multivariate analysis of TTR revealed the SLC29A1 rs693955 CC genotype and first induction failure to be significantly associated with a shorter TTR. The DCTD rs9990999 AG/GG and SLC29A1 rs693955 CC genotypes were also significantly associated with shorter duration of neutropenia. The results of our study suggest that SNP analysis can be an important tool in improving drug responsiveness and enabling a better understanding of this condition and the development of tailor-made treatments for AML patients who benefit from consolidated high-dose Ara-C therapy.
Division of Hematology/Oncology, Department of Internal Medicine, Tokai University School of Medicine, 143 shimokasuya, Isehara, Kanagawa, 259-1143, Japan.
Jun
J
Amaki
Makoto
M
Onizuka
Ken
K
Ohmachi
Yasuyuki
Y
Aoyama
Ryujiro
R
Hara
Akifumi
A
Ichiki
Hidetsugu
H
Kawai
Ai
A
Sato
Mitsuki
M
Miyamoto
Masako
M
Toyosaki
Shinichiro
S
Machida
Minoru
M
Kojima
Yukari
Y
Shirasugi
Hiroshi
H
Kawada
Yoshiaki
Y
Ogawa
Kiyoshi
K
Ando
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016896:Treatment Outcome; D055815:Young Adult
D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine