Abstract:
Acute lymphoblastic leukemia (ALL) is the most common malignancy affecting
children in Zimbabwe and 6-mercaptopurine is frequently used as part of its treatment. However, 6-
mercaptopurine is associated with side-effects such as severe neutropenia (a condition where you have
a low number of white blood cells called neutrophils in your blood), with increased risk observed in
patients carrying variants in genes involved in the metabolism of 6-mercaptopurine. Therefore, this study
aimed to determine the frequency of polymorphisms in speci!c genes as well as their association with
drug intolerance. A total of 41 patients on ALL treatment were studied. Review of treatment records
was done to determine the cumulative 6-mercaptopurine dose and calculate dose intensity. Genotyping
(to determine the versions of a gene a patient carries) for TPMT and NUDT15 (rs116855232) was
performed and results correlated with drug dose intensity. The most frequent genotype was TPMT*1/*1,
occurring in 80% of the participants. The remaining 20% were carriers with two different copies of TPMT
(*1/*3C). The defective TPMT*3C variation occurred at 9.8% and none had TPMT*2, *3A, *3B or NUDT15
rs116855232 variants. Comparison analysis with dose intensity was done for 23 participants (56%) who
had maintenance records available. The median dose intensity of 47% for TPMT*1/*3C participants was
considerably low when compared to that of a normal TPMT*1/*1 patient, which was 77%. However, no
statistically signi!cant difference was observed between TPMT genotype and dose intensity. This is the !rst
study in a group of leukemic Zimbabweans to investigate the frequency of TPMT and NUDT15 variants.
With a high variation frequency of 9.8% for the defective TPMT*3C, pharmacogenetics testing for TPMT
before treatment with 6-MP is recommended in the Zimbabwean population
