| 杜成成,韩蕊,王媛,等.NUDT15 c.415C>T和 TPMT*3C基因多态性与儿童急性淋巴细胞白血病诱导期 6-巯基嘌呤耐受性相关性研究[J].安徽医药,2025,29(3):591-595. |
| NUDT15 c.415C>T和 TPMT*3C基因多态性与儿童急性淋巴细胞白血病诱导期 6-巯基嘌呤耐受性相关性研究 |
| The correlation between NUDT15 c.415C>T and TPMT*3C gene polymorphisms and 6-MP tolerance during induction chemotherapy in children with acute lymphoblastic leukemia |
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| DOI：10.3969/j.issn.1009-6469.2025.03.032 |
| 中文关键词: 急性淋巴细胞白血病 核苷二磷酸 X成份型基元 15 硫嘌呤甲基转移酶 基因多态性 6-巯基嘌呤 儿童 |
| 英文关键词: Acute lymphoblastic leukemia Nucleoside diphosphate X-component motif 15 Thiopurine S-methyhransferase Gene polymorphism 6-Mercaptopurine Child |
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| 目的探讨核苷二磷酸连接的 X成份型基元 15(NUDT15)c.415C>T rs116855232和硫嘌呤甲基转移酶( TPMT)*3C rs1142345基因多态性与儿童急性淋巴细胞白血病( ALL)病儿 6-巯基嘌呤( 6-MP)耐受性的关系。方法选取 2019年 9月至 2022年 11月在徐州市儿童医院确诊 54例 ALL病儿为研究对象，所有病儿均进行 TPMT*3C和 NUDT15 c.415C>T多态性的基因分型。结合临床资料，分析 TPMT和 NUDT15基因多态性对儿童 ALL诱导期治疗中 6-MP耐受性的影响。结果 54例病儿中 B细胞(B)-ALL 47例( 87.04%)、T细胞(T)-ALL 7例(12.96%)。通过限制性片段长度多态性聚合酶链反应( PCR-RFLP)确定的基因型分布为: NUDT15 rs116855232位点包括 CC野生型 45例( 83.3%)CT杂合型 7例( 13.0%)TT纯合型 2例( 3.7%)等位基因变异频率为 10.2%；TPMT*3C rs1142345位点包括 AA野生型 51例( 94.4%)，AG杂合型 3例( 5.6%)，，等位基因变异频率为，2.8%。 NUDT15 rs116855232突变组( CT+TT型)白细胞计数 <1×109/L的持续时间长于，野生型组( CC型)(P=0.001)；突变型组血小板的输注量 10(0，20)U多于野生组 0(0，10)U(P=0.022)；突变型组中性粒细胞绝对计数 <0.5×109/L的持续时间 9(4，17)d长于野生型组 6(3，9)d(P=0.036)。结论 NUDT15 rs116855232基因多态性可以影响儿童 ALL病儿对 6-MP的耐受性。在有条件的情况下，对病儿进行治疗前的 NUDT15基因型检测，优化 6-MP使用剂量，有助于减少严重骨髓抑制持续时间和血液制品输注量。 |
| 英文摘要: |
| Objective To explore the correlation between nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) c.415C> T rs116855232 and thiopurine methyltransferase (TPMT)*3C rs1142345 gene polymorphisms with 6-mercaptopurine (6-MP) tolerance in children with childhood acute lymphoblastic leukemia (ALL).Methods A total of 54 children with ALL diagnosed in Xuzhou Chil-dren's Hospital from September 2019 to November 2022 were selected as the research objects, all of whom were genotyped by TPMT*3C and NUDT15 c.415C>T polymorphisms. In combination with clinical data, the effects of TPMT and NUDT15 gene polymorphismson the tolerance of 6-MP during induction chemotherapy for childhood ALL were analyzed. Results Among the 54 children, 47 (87.04%) children had B-cell (B)-ALL and 7 (12.96%) children had T-cell (T) -ALL. Genotype distribution was determined by poly-merase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The counts of CC, CT and TT genotypes for NUDT15rs116855232 were 45 (83.3%), 7 (13.0%) and 2 (3.7%), respectively. The frequency of allelic variation was 10.2% for NUDT15rs116855232. The counts of AA and AG genotypes for TPMT*3C rs1142345 were 51 (94.4%) and 3 (5.6%), respectively. The frequen-cy of allelic variation was 2.8% for TPMT*3C rs1142345. The NUDT15 rs116855232 mutant group (CT+TT genotype) exhibited a sig-nificantly longer duration of WBC count <1×109/L compared with the wild-type group (CC genotype) (P=0.001). The median platelet in-fusion amount was higher in the mutant group than in the wild-type group [10 (0, 20) U vs. 0 (0, 10) U] (P=0.022). Additionally, the me-dian duration of absolute neutrophil count <0.5×109/L was longer in the mutant group compared to the wild-type group [9 (4, 17) d vs. 6 (3, 9) d] (P=0.036).Conclusions NUDT15 rs116855232 gene polymorphism can influence the tolerance of 6-MP in the treatment of childhood ALL. If allowed, NUDT15 genotype identification is done before treatment in order to optimize the dose of 6-MP, which helps to shorten severe myelosuppression and lower the volume of blood product infusion. |
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