[Influence of hOCT1 polymorphism on imatinib mesylate effectiveness in chronic myelogenous leukemia patients].
OBJECTIVE
To explore the correlation between hOCT1 polymorphism and imatinib mesylate (IM) effectiveness in chronic myelogenous leukemia(CML) patients, and to provide for the clinical individual personalized therapy.


METHODS
Fifty-three CML and 23 non-CML patients were enrolled in this study. Blood or bone marrow samples were collected. Amplification refractory mutation system (ARMS)-polymerase chain reaction was used to amplify the polymorphisms gene segment of hOCT1-P283L, R287G and M408V and their frequencies were statistically analysed. With clinical outcomes, the correlation between hOCT1 polymorphism and IM effectiveness in CML was analyzed.


RESULTS
(1) For 74 Han Chinese, the allele frequencies of hOCT1-P283L, R287G and M408V were 39.86%, 29.05% and 45.27%, respectively. (2) The genotypes of hOCT1-P283L, R287G and M408V in 2 Tibetan Chinese were CC, CC, AG and CC, CG, AG, respectively. (3) In the CML patients with IM optimal response, the frequencies of 283T and 287G allele were predominant (P<0.05). No significant difference was found in the frequency distribution of hOCT1-M408V genotype and allele among the 3 different response groups (P>0.05).


CONCLUSIONS
(1) Three single nucleotide polymorphisms (cSNP) P283L, R287G and M408V were found in the hOCT1 gene from 76 Chinese. (2) hOCT1 gene polymorphism is associated with the long-term molecular response of CML patients received IM therapy, indicating that the polymorphisms of hOCT1-283T, 287G may be good predictors for IM response. (3) There is no correlation between the polymorphisms of hOCT1-P283L, R287G, M408V and secondary IM resistance in CML patients.
Hu
Nan
N
Hematology Department, West China Hospital, Sichuan University, Chengdu 610041, China.
Zhu
Huan-ling
HL
Liu
Heng-wei
HW
Zeng
Chun-xue
CX
Meng
Wen-tong
WT
Liu
Ting
T
D001549:Benzamides; D005260:Female; D005787:Gene Frequency; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D027702:Organic Cation Transporter 1 / Q000235:genetics*; D010879:Piperazines / Q000627:therapeutic use*; D011110:Polymorphism, Genetic; D011743:Pyrimidines / Q000627:therapeutic use*; D016896:Treatment Outcome
D001549:Benzamides; D027702:Organic Cation Transporter 1; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate