AN INVESTIGATION INTO THE MECHANISM OF L-ASPARAGINASE RESISTANCE IN L5178Y MURINE LEUKEMIA-CELLS

Resistance of leukemia cells to L-asparaginase is presumed to be due t o increased expression of asparagine synthetase activity by resistant cells, so they are no longer dependent on an exogenous source of L-asp aragine for growth. The mechanism by which cells acquire the ability f or increased enzyme expression, however, has not been clearly defined. Evidence presented here indicates that genomic alterations in the for m of translocations, gene amplification, or increased P-glycoprotein e xpression, do not account for the phenotypic transformation from L-asp araginase sensitivity to L-asparaginase resistance. Instead, both sens itive and resistant L5178Y cells contain immunoreactive material detec ted by Western blotting with an antiserum prepared against bovine panc reatic asparagine synthetase. This suggests that the mechanism of resi stance might involve modification of asparagine synthetase in L-aspara ginase-resistant cells by an as-yet-unidentified mechanism or by inhib ition of enzyme activity in the L-asparaginase-sensitive cells.