ALLOPURINOL INHIBITS DE-NOVO PURINE SYNTHESIS IN LYMPHOBLASTS OF CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIA

Allopurinol is used to prevent hyperuricemia in newly diagnosed patien ts with acute lymphoblastic leukemia (ALL). Although allopurinol has b een shown to inhibit de novo purine synthesis (DNPS) in fibroblasts in vitro, this effect has not been assessed in ALL lymphoblasts. We asse ssed DNPS in ALL lymphoblasts in 46 consecutive patients with ALL. DNP S was determined by C-14-formate incorporation in purine bases both at diagnosis (n = 46) and 44 h after MIX therapy +/- allopurinol (n = 31 ). The 27 patients who had received no allopurinol prior to the diagno stic bone marrow aspirate had significantly higher rates of DNPS (medi an, 102 fmol new purines/nmol total purines/h) compared to the 12 pati ents who had received more than one dose of allopurinol (100 mg/m(2) o rally) (median, 2.3 fmol/nmol/h; P < 0.001); the seven patients who re ceived one dose of allopurinol had intermediate rates of DNPS (median, 58.5 fmol/nmol/h). Among patients who were evaluable for MTX effects at 44 h (n = 31), the percent inhibition of DNPS was greater in the ei ght patients who received concomitant allopurinol (median, 100% inhibi tion) compared to the 23 patients who received only methotrexate thera py (median, 89% inhibition, P = 0.03). These data indicate that allopu rinol suppresses DNPS in ALL lymphoblasts in vivo, an effect that may contribute to the decrease in circulating blasts in patients with newl y diagnosed acute leukemias.