Cheng Juan, Zhang Hao, Ma Hai-Zhen, Li Juan
Department of Hematology, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
Department of Central Laboratory, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China.
Exp Ther Med. 2019 May;17(5):4285-4288. doi: 10.3892/etm.2019.7434. Epub 2019 Mar 26.
As an essential component of consolidation and maintenance therapy for acute lymphoblastic leukemia (ALL), mercaptopurine (6-MP) causes critical myelosuppression. The current study aimed to clarify the reasons for severe myelosuppression and significant hyperpigmentationin a patient with ALL that received consolidation therapy. The present study performed patient NUDT15 testing with fluorescence hybridization and whole-exome sequencing. The results revealed that the patient was a homozygous carrier (415C>T, TT) for rs116855232 (NUDT15). The dose of 6-MP was adjusted down from 30%, with the patient receiving maintenance therapy at 8% of the recommended dose. The homozygous mutant (TT genotype) of NUDT15 may cause hematopoietic toxicity with low doses of 6-MP. NUDT15 genotyping should therefore be performed prior to the administration of thiopurine, the dosage of which requires adjustment.
作为急性淋巴细胞白血病（ALL）巩固和维持治疗的重要组成部分，巯嘌呤（6-MP）会导致严重的骨髓抑制。本研究旨在阐明一名接受巩固治疗的ALL患者出现严重骨髓抑制和显著色素沉着的原因。本研究采用荧光杂交和全外显子测序对患者进行NUDT15检测。结果显示，该患者是rs116855232（NUDT15）的纯合子携带者（415C>T，TT）。6-MP剂量从30%下调，患者接受推荐剂量8%的维持治疗。NUDT15的纯合突变体（TT基因型）可能导致低剂量6-MP产生造血毒性。因此，在给予硫嘌呤之前应进行NUDT15基因分型，其剂量需要调整。
