Department of Hematology, Faculty of Medicine, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam.
Ho Chi Minh City Blood Transfusion and Hematology Hospital, Ho Chi Minh City, Vietnam.
Pediatr Hematol Oncol. 2022 Sep;39(6):561-570. doi: 10.1080/08880018.2022.2035027. Epub 2022 Feb 14.
6-mercaptopurine (6-MP) plays a critical role in the treatment of pediatric acute lymphoblastic leukemia (ALL). and gene variants have been strongly associated with myelotoxicity caused by using 6-MP. Therefore, the purpose of this study is to investigate the frequency of and polymorphisms, as well as the impact of variants on the use of 6-MP to treat pediatric ALL in Vietnam. Sanger sequencing was applied to detect and gene variants in 70 pediatric ALL patients. Duration of drug interruption, level of neutropenia, and 6-MP tolerance dose were recorded. variants were detected from 23 out of 70 (32.9%) patients. Three well-known haplotype variants were identified as *2 (p.V18_V19insGV and p.R139C), *3 (p.R139C), and *6 (p.V18_V19insGV); besides, a novel p.R11Q was not previously reported. The wild-type, heterozygous variant, and homozygous variant genotypes were 67.1%, 30.1%, and 2.8%, respectively. Two heterozygous polymorphisms were *3C and *6, accounted for 2.8%. Patients with intermediate and low activity NUDT15 were given the median 6-MP tolerance dose of 55.2 and 37.2 versus 69.5 mg/m/day of patients with NUDT15 normal activity ( = 0.0001). Patients with homozygous variant diplotype were drastically sensitive to 6-MP, with an average dose intensity of 49.6%, compared to 73.6% and 92.7% of those with heterozygous and wild-type diplotype, respectively ( = 0.0001). Our results suggest that 6-MP dose adjustment should be based on variants in pediatric Vietnamese ALL patients.
6-巯基嘌呤（6-MP）在治疗小儿急性淋巴细胞白血病（ALL）中起着关键作用。 和 基因变异与使用 6-MP 引起的骨髓抑制有很强的关联。因此，本研究的目的是调查 和 基因多态性的频率，以及 变异对越南小儿 ALL 使用 6-MP 治疗的影响。应用 Sanger 测序法检测 70 例小儿 ALL 患者的 和 基因变异。记录药物中断时间、中性粒细胞减少程度和 6-MP 耐受剂量。从 70 例患者中的 23 例（32.9%）检测到 变异。鉴定出三种众所周知的单倍型变异，分别为 *2（p.V18_V19insGV 和 p.R139C）、*3（p.R139C）和 *6（p.V18_V19insGV）；此外，还发现了一种新的 p.R11Q 变异，以前未报道过。 野生型、杂合变异型和纯合变异型基因型分别为 67.1%、30.1%和 2.8%。两种 杂合多态性为 *3C 和 *6，占 2.8%。中低活性 NUDT15 的患者给予 6-MP 耐受剂量的中位数分别为 55.2 和 37.2mg/m/天，而 NUDT15 正常活性的患者为 69.5mg/m/天（ = 0.0001）。纯合变异二倍体患者对 6-MP 极为敏感，平均剂量强度为 49.6%，而杂合和野生型二倍体患者分别为 73.6%和 92.7%（ = 0.0001）。我们的结果表明，应根据小儿越南 ALL 患者的 变异来调整 6-MP 剂量。
