Metabolites of mercaptopurine in red blood cells: a relationship between 6-thioguanine nucleotides and 6-methylmercaptopurine metabolite concentrations in children with lymphoblastic leukemia

Intracellular concentrations of 6-mercaptopurine metabolites, i.e. of 6-thi oguanine nucleotides (6-TGN) and of 6-methylmercaptopurine metabolites (6-m MP) were analysed in red blood cells (RBC) of 19 children with acute lympho blastic leukemia (ALL), the subjects of a maintenance chemotherapy of their first remission. Interpatient variations in concentrations of both metabol ites were high; concentrations of 6-TGN varied from <60 to 833 pmo1/8x10(8) RBC (median value, 144) and those of 6-mMP metabolites from <150 to 19 000 pmol/8x10(8) RBC (median value, 3250). In two patients, 6-TGN appeared at concentrations below the limits of assay sensitivity, and 6-mMP metabolites were not detected. In another child the concentrations of both metabolites were at the limit of the assay sensitivity. In three other children the co ncentrations of both metabolites were below the median value of the group. In the analysed group of children, significant correlations were found betw een the white cell count (WBC) and RBC 6-TGN (r(s) = -0.72, P<0.005) as wel l as between the neutrophil count and RBC 6-TGN (r(s) = -0.60, P<0.01). No significant correlation was found between the concentrations of 6-TGN and 6 -mMP metabolites. The monitoring of concentrations of 6-TGN as well as of 6 -mMP metabolites allows an early identification of patients who are at an i ncreased risk of the disease relapse as indicated by the low levels of eith er 6-TGN itself or of its two metabolites. (C) 1999 Elsevier Science B.V. A ll rights reserved.