title: Prognostic significance of the null genotype of glutathione S-transferase-T1 in patients with acute myeloid leukemia: increased early death after chemotherapy.
abstract: We investigated the prognostic significance of genetic polymorphism in glutathione-S transferase mu 1 (GSTM1), glutathione-S transferase theta 1 (GSTT1), NAD(P)H:quinone oxidoreductase (NQO1) and myeloperoxidase (MPO), the products of which are associated with drug metabolism as well as with detoxication, in 193 patients with de novo acute myeloid leukemia (AML) other than M3. Of the patients, 64.2% were either homozygous or heterozygous for GSTT1 (GSTT1(+)), while 35.8% showed homozygous deletions of GSTT1 (GSTT1(-)). The GSTT1(-) group had a worse prognosis than the GSTT1(+) group (P = 0.04), whereas other genotypes did not affect the outcome. Multivariate analysis revealed that GSTT1(-) was an independent prognostic factor for overall survival (relative risk: 1.53; P = 0.026) but not for disease-free survival of 140 patients who achieved complete remission (CR). The rate of early death after the initiation of chemotherapy was higher in the GSTT1(-) group than the GSTT1(+) group (within 45 days after initial chemotherapy, P = 0.073; within 120 days, P = 0.028), whereas CR rates and relapse frequencies were similar. The null genotype of GSTT1 might be associated with increased toxicity after chemotherapy.
authors.affiliation: Department of Infectious Diseases, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Naoe
authors.forename: Y
authors.initials: Y
authors.lastname: Tagawa
authors.forename: H
authors.initials: H
authors.lastname: Kiyoi
authors.forename: Y
authors.initials: Y
authors.lastname: Kodera
authors.forename: S
authors.initials: S
authors.lastname: Miyawaki
authors.forename: N
authors.initials: N
authors.lastname: Asou
authors.forename: K
authors.initials: K
authors.lastname: Kuriyama
authors.forename: S
authors.initials: S
authors.lastname: Kusumoto
authors.forename: C
authors.initials: C
authors.lastname: Shimazaki
authors.forename: K
authors.initials: K
authors.lastname: Saito
authors.forename: H
authors.initials: H
authors.lastname: Akiyama
authors.forename: T
authors.initials: T
authors.lastname: Motoji
authors.forename: M
authors.initials: M
authors.lastname: Nishimura
authors.forename: K
authors.initials: K
authors.lastname: Shinagawa
authors.forename: R
authors.initials: R
authors.lastname: Ueda
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: R
authors.initials: R
authors.lastname: Ohno
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D003561:Cytarabine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D003630:Daunorubicin / Q000008:administration & dosage; D018572:Disease-Free Survival; D005047:Etoposide / Q000008:administration & dosage; D005500:Follow-Up Studies; D017353:Gene Deletion; D005838:Genotype; D005982:Glutathione Transferase / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D007951:Leukemia, Myeloid / Q000097:blood / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000401:mortality; D015122:Mercaptopurine / Q000008:administration & dosage; D015999:Multivariate Analysis; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000097:blood / Q000235:genetics; D009363:Neoplasm Proteins / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D009195:Peroxidase / Q000097:blood / Q000235:genetics; D011110:Polymorphism, Genetic; D011239:Prednisolone / Q000008:administration & dosage; D011379:Prognosis; D012074:Remission Induction; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D007527:Isoenzymes; D009363:Neoplasm Proteins; D003561:Cytarabine; D005047:Etoposide; D011239:Prednisolone; C015019:enocitabine; D015122:Mercaptopurine; D009195:Peroxidase; D016660:NAD(P)H Dehydrogenase (Quinone); C413545:glutathione S-transferase T1; D005982:Glutathione Transferase; D003630:Daunorubicin