Homozygous mutation in NUDT15 in childhood acute lymphoblastic leukemia with increased susceptibility to mercaptopurine toxicity: A case report

Abstract

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 in situ 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.

Keywords: childhood acute lymphoblastic leukemia; mercaptopurine; nudix hydrolase 15; toxicity.

Figure 1.

Hyperpigmentation clinical presentation in hands. (A) Normal control. (B) Two weeks post-early intensification chemotherapy with 6-MP (60 mg/m²/day). (C) Two weeks post-consolidation and delayed intensification chemotherapy with 6-MP (6 mg/m²/day). 6-MP, mercaptopurine.

Figure 2.

NUDT15 mutation analysis results demonstrated that the patient was a homozygous carrier (415C>T, TT) for rs116855232. (A) NUDT15 gene amplification testing by fluorescence in situ hybridization. (B) Whole exome sequencing was used to identify the NUDT15 variant was chr13: 48619855 NUDT15: 415C>T. NUDT15, nudix hydrolase 15; chr, chromosome.