Action and Sequence Dependent Interaction of Acivicin and 6-Thioguanine in Human Derived Malignant T-All and Calla+ Cell Lines

Abstract

Acivicin is an irreversible inhibitor of L-glutamine amino transferases and therefore effects several enzymatic steps in purine de novo sythesis (PDNS) including phosphoribosyl pyrophosphate (PRPP) amidotransferase and enzymes which are specifically rate limiting for GTP, for example, GMP synthetase. This drug biochemically targets GTP concentration in leukemic blast cells (fig. 1)¹. Acivicin may also be effective as a modulator of other anti-leukemic agents such as AraC and 6-thioguanine (6TG).² Acivicin interferes with PDNS resulting in PRPP elevations which may allow for synergistic action with antipurines.³ In response to inhibition of (PDNS), an increase in the availability of 5-phosphoribosyl-1-pyrophosphate (PRPP) occurs. As a result of this increased availability of PRPP potentiation of 6TG incorporation can be expected in cells with an active PDNS.