Hao Q S, Wang Z, Fang Q Y, Gong X Y, Liu K Q, Li Y, Wei H, Wang Y, Li Q H, Wang M, Tian Z, Wang J X, Mi Y C
Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Tianjin 300020.
Zhonghua Xue Ye Xue Za Zhi. 2021 Nov 14;42(11):911-916. doi: 10.3760/cma.j.issn.0253-2727.2021.11.005.
To investigate the effect of genetic polymorphisms of TPMT2 rs1800462, TPMT3B rs1800460, TPMT3C rs1142345, and NUDT15 rs116855232 on the tolerance of 6-mercaptopurine (6-MP) therapy in adult acute lymphoblastic leukemia (ALL) . A total of 216 adult patients who were diagnosed with ALL and treated with cyclophosphamide, cytarabine, and 6-MP [complementary and alternative medicine (CAM) regimen] from September 2015 to December 2019 were included. Polymorphisms were detected by TaqMan SNP Genotyping Assay. Combined with clinical data, the influence of genetic polymorphism on the tolerance of 6-MP in the treatment of ALL was analyzed. Among the 216 patients, 185 (85.65%) patients had B-ALL and 31 (14.35%) patients had T-ALL. 216 (100%) patients had CC genotype for both TPMT2 rs1800462 and TPMT3B rs1800460. The number of TT and TC genotypes for TPMT3C rs1142345 was 209 (96.76%) and 7 (3.24%) , respectively. The allele frequency was 1.62% for TPMT3C rs1142345. The number of CC, CT, and TT genotypes for NUDT15 rs116855232 was 166 (76.85%) , 48 (22.22%) , and 2 (0.93%) , respectively. The allele frequency was 12.04% for NUDT15 rs116855232. The TPMT3C rs1142345 mutant group (TC+CC genotype) had less transfusion volume of packed red blood cell than the wild group (CC genotype) (=0.036) , and the mutant group (TC+CC genotype) had a higher risk to develop hepatotoxicity (increased aspartate aminotransferase) than the wild group (CC genotype) (=9.559, 95% 1.135-80.475, =0.038) . The durations of white blood cells (WBC) <1×10(9)/L and absolute neutrophil count (ANC) <0.5×10(9)/L in the NUDT15 rs116855232 mutation group (CT+TT genotype) were longer than that in the wild group (CC genotype) (=0.005, =0.007) , and the transfusion volume of apheresis-derived platelets in the mutant group (CT+TT type) was greater than that in the wild group (CC genotype) (=0.014) . Genetic polymorphism of TMPT and NUDT15 has an effect on the tolerance of 6-MP in the treatment of adult ALL. Detecting genotypes of patients with ALL before treatment helps to optimize the dosage of 6-MP, which may help shorten the bone marrow suppression duration and reduce blood transfusion volume.
研究TPMT2 rs1800462、TPMT3B rs1800460、TPMT3C rs1142345和NUDT15 rs116855232基因多态性对成人急性淋巴细胞白血病（ALL）患者6-巯基嘌呤（6-MP）治疗耐受性的影响。纳入2015年9月至2019年12月期间共216例诊断为ALL并接受环磷酰胺、阿糖胞苷和6-MP[补充和替代医学（CAM）方案]治疗的成年患者。采用TaqMan SNP基因分型检测法检测基因多态性。结合临床资料，分析基因多态性对ALL患者6-MP治疗耐受性的影响。216例患者中，185例（85.65%）为B-ALL，31例（14.35%）为T-ALL。TPMT2 rs1800462和TPMT3B rs1800460的216例（100%）患者均为CC基因型。TPMT3C rs1142345的TT和TC基因型数量分别为209例（96.76%）和7例（3.24%）。TPMT3C rs1142345的等位基因频率为1.62%。NUDT15 rs116855232的CC、CT和TT基因型数量分别为166例（76.85%）、48例（22.22%）和2例（0.93%）。NUDT15 rs116855232的等位基因频率为12.04%。TPMT3C rs1142345突变组（TC+CC基因型）的浓缩红细胞输血量低于野生组（CC基因型）（=0.036），且突变组（TC+CC基因型）发生肝毒性（天冬氨酸转氨酶升高）的风险高于野生组（CC基因型）（=9.559，95% 1.135 - 80.475，=0.038）。NUDT15 rs116855232突变组（CT+TT基因型）白细胞（WBC）<1×10⁹/L和绝对中性粒细胞计数（ANC）<0.5×10⁹/L的持续时间长于野生组（CC基因型）（=0.005，=0.007），且突变组（CT+TT型）的单采血小板输血量大于野生组（CC基因型）（=0.014）。TMPT和NUDT15基因多态性对成人ALL患者6-MP治疗耐受性有影响。治疗前检测ALL患者的基因型有助于优化6-MP剂量，这可能有助于缩短骨髓抑制持续时间并减少输血量。
