[The effects of glutathione S-transferase (GSTT1 and GSTM1) genes polymorphisms on treatment efficacy and prognosis of acute myeloid leukemia].
OBJECTIVE
To investigate the impact of GSTT1 and GSTM1 genotypes on response, drug side effects and prognosis of acute myeloid leukemia (AML).


METHODS
GSTT1 and GSTM1 genotypes were analysed in 180 AML patients with PCR. Complete remission (CR) rate, drug side-effects, overall survival, relapse-free survival and relapse rate were compared in groups with or without GSTT1 and GSTM1 genes.


RESULTS
(1) The CR rate (96.9%) in GSTT1 and GSTM1 genes double-present patients was significantly higher than that in patients of GSTT1 null or GSTM1 null (CR rate 78.0%) (P = 0.013). The risk of failure to achieve CR in patients with GSTT1 null/GSTM1 null is 8.736 times higher than that in patients with GSTT1 and GSTM1 genes double-present (odds ratio OR was 8.736, 95% CI was 1.146 - 66.574). The CR rate (88.4%) in GSTT1 present patients was also significantly higher than that in patients of GSTT1 null (CR rate 74.7%) (P = 0.021, OR = 2.572, 95% CI 1.136 - 5.826). (2) There was no significant relationship between GSTT1/GSTM1 genotypes and the lasting time of neutrophilic granulocyte (ANC) < 0.5 x 10(9)/L and PLT < 20 x 10(9)/L. The risk of ALT abnormality in patients with GSTM1 null is 2.593 times higher than that in patients with GSTM1 present (P = 0.016, 95% CI 1.176 - 5.717). (3) Overall survival and relapse-free survival of GSTT1 and GSTM1 double-present patients were significantly better than those in patients of GSTT1 null/GSTM1 null (mean overall survival was 68.4 months vs 38.5 months, P = 0.028, and mean relapse-free survival was 73.5 months vs 34.9 months, P = 0.014, respectively). Relapse-free survival in GSTT1 null patients was significantly shorter than that in patients with GSTT1 present (26.7 months vs 64.3 months, P = 0.038), but there was no significant difference of overall survival between the two groups. The relapse rate of double-present patients was significantly lower than that of GSTT1 null/GSTM1 null patients (13.3% vs 35.6%, P = 0.019).


CONCLUSIONS
GSTT1 and GSTM1 genotypes were apparently related with response, drug side effects and prognosis of patients with AML. GSTT1 and GSTM1 genotype might be useful in selecting appropriate chemotherapy regimens for patients with AML.
Zhang
Yue
Y
Institute of Hematology, Chinese Academe of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
Yang
Lin
L
Li
Rui
R
Zhang
Li
L
Zhang
Mei-rong
MR
Xiao
Zhi-jian
ZJ
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis
D000970:Antineoplastic Agents; D005982:Glutathione Transferase; C413545:glutathione S-transferase T1