NUDT15 c.415C>T increases risk of 6-mercaptopurine induced myelosuppression during maintenance therapy in children with acute lymphoblastic leukemia

NUDT15 c.415C>T increases risk of 6-mercaptopurine induced myelosuppression during maintenance therapy in children with acute lymphoblastic leukemia

Kanhatai Chiengthong (2016) Haematologica (Link to abstract)                                                             


This manuscript reports the effect of single nucleotide polymorphisms in ITPA and NUDT15 in a cohort of 82 pediatric ALL patients from Thailand. ITPA polymorphisms showed no difference in 6MP induced myelosuppression, and no difference in cumulative 6MP doses.  Of the NUDT15 c.415 polymorphisms, 70 (85.4%), 10(12.2%), and 2 (2.4%) patients were CC, CT, and TT, respectively. NUDT15 c.415C>T was strongly associated with 6-MP induced early myelosuppression. Adjustment of 6MP doses according to blood counts resulted in lower median cumulative doses in NUDT15 c.415 CT and TT of 45% and 80%, respectively, compared to CC genotype. These results are consistent with results from Korean and Japanese studies (Yang, JCO 2015).


* Dose adjustments of 6MP in ALL treatment based on polymorphisms in TPMT gene is well established. However, these TPMT variants are infrequent in most Asian populations and this article contributes to the understanding of NUDT15 polymorphisms in adjusting 6MP in Asian ethnicities.