SOMATIC MUTATIONS AT T-CELL ANTIGEN RECEPTOR AND GLYCOPHORIN-A LOCI IN PEDIATRIC LEUKEMIA PATIENTS FOLLOWING CHEMOTHERAPY - COMPARISON WITHHPRT LOCUS MUTATION

Frequencies of somatic mutations in pediatric patients with leukemia w ere evaluated following intensive treatment at three different loci: t he hypoxanthine-guanine phosphoribosyl transferase (HPRT), T-cell anti gen receptor (TCR), and glycophorin A (GPA) gene. Thirty-two children with acute lymphoblastic leukemia (ALL), nine children with acute myel ogenous leukemia (AML), and 20 age-matched healthy controls were inclu ded in the study of mutant frequencies (Mfs) at the HPRT and TCR loci. Among these patients and controls, individuals with heterozygous MN b lood type, i.e., 14 children with ALL, three children with AML, and ni ne healthy controls, served for the further assessment of variant freq uency (Vf) at the GPA locus. In ALL patients, geometric mean Mfs and V fs at these loci were significantly higher than in healthy controls. T he high Mf value at the HPRT locus persisted for up to 8 years after t he end of chemotherapy. On the other hand, the Mf values at the TCR lo cus and Vf values at the GPA locus declined gradually with time. In AM L patients, on the other hand, the geometric mean Mf only at the TCR l ocus was significantly higher than in the controls, albeit to a lesser degree than in ALL patients. These data suggest that anti-cancer ther apy induces somatic mutations at various loci and that ALL patients ar e more susceptible to mutagenic intervention than are AML patients.