1.Association of polymorphisms of cytosine arabinoside-metabolizing enzyme gene with therapeutic efficacy for acute myeloid leukemia.
Pei-Pei XU ; Bao-An CHEN ; Ji-Feng FENG ; Lu CHENG ; Guo-Hua XIA ; Yu-Feng LI ; Jun QIAN ; Jia-Hua DING ; Zu-Hong LU ; Xue-Mei WANG ; Ke XU ; Margaret SCHULTZ
Chinese Medical Journal 2012;125(12):2137-2143
BACKGROUNDThe cytosine arabinoside (Ara-C)-based chemotherapy is the major remedial measure for acute myeloid leukemia (AML). Deoxycytidine kinase (DCK) and cytidine deaminase (CDA) are the key enzymes in the metabolism of Ara-C. Many single nucleotide polymorphisms (SNPs) and haplotypes of DCK and CDA, which contribute to susceptibility to Ara-C, have been identified in Africans and Europeans. However, there has been no report about the relation among three SNPs in DCK (rs115543896, rs72552079, and rs111454937) and two SNPs in CDA (rs2072671 and rs60369023), and their clinical response to Ara-C for a Chinese population. In this study, we aimed to investigate whether these five SNPs are associated with the therapeutic outcomes of Ara-C-based chemotherapy regimens in patients with AML.
METHODSA total of 151 Chinese patients with AML were enrolled in our study. SNPs genotyping were performed using the MassARRAY system by means of the matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF-MS) method.
RESULTSThe results illustrated that DCKrs111454937 AA genotype was more frequent in patients with higher platelet count, and A allele frequency was significantly higher in the group £40 years, lower white blood cell (WBC) count patients group and the group with platelet counts > 60'10(9)/L. Meanwhile, both DCKrs72552079 TC (OR = 1.225, 95%CI = 1.225 - 9.851, P = 0.0192) and CDArs60369023 GA (OR = 9.851, 95%CI = 1.31 - 77.93, P = 0.0263) significantly improved Ara-C-based chemotherapy response. While DCKrs11554389 AA (OR = 0.147, 95%CI = 0.027 - 0.801, P = 0.0267) was associated with the decrease of Ara-C-based chemotherapy response.
CONCLUSIONIt is evident that the DCK and CDA polymorphisms might be the important markers for the AML patients' therapy outcomes in a Chinese population.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cytarabine ; therapeutic use ; Cytidine Deaminase ; genetics ; Deoxycytidine Kinase ; genetics ; Female ; Gene Frequency ; genetics ; Humans ; Leukemia, Myeloid, Acute ; drug therapy ; genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; genetics ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Treatment Outcome ; Young Adult
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