Relationship Between Thiopurine S-Methyltransferase Genotype and Phenotype in Pediatric Acute Lymphoblastic Leukemia in Addis Ababa, Ethiopia.

Objective: Thiopurine S-methyltransferase (TPMT) is a cytosolic transmethylase enzyme that catalyzes the S-methylation of thiopurine drugs, the mainstay of acute lymphoblastic leukemia treatment. TPMT enzyme activity shows interindividual variability, which can partly be explained by genetic variants in the TPMT gene. In this study, we aimed to investigate the concordance between genotype and phenotype of TPMT gene in a cohort of patients with acute lymphoblastic leukemia from Ethiopia.

Methods: In the present study, 73 on treatment and 32 treatment completed patients were included. TPMT activity was measured in whole blood of the participant by HPLC. The enzyme activity was expressed both in nmol6MTG/gHb/h and mU/L. The 3 most common variants in the TPMT gene (238G>C, 460G>A, and 719A>G) were genotyped.

Results: Only 2 patients carried the *3C variant (719A>C) (both heterozygous), no other variants were detected. In the treatment group, TPMT activity (nmol6MTG/gHb/h) was significantly higher than the treatment completed group (32 vs 25.55, p = 0.018). In the treatment group TPMT activity (nmol6MTG/gHb/h) was significantly higher in individuals with Hb < 12 g/dL compared with individuals with Hb ≥ 12 g/dL (34.05 vs 27, p = 0.037).

Conclusions: This study showed that the commonly genotyped variants in TPMT are rare in pediatric acute lymphoblastic leukemia patients from Ethiopia.