Taken together, the results showed that chemical modification with carboxymethyl dextran brings about improvement of biochemical properties through several changes in the structural attributes of l-asparaginase and might enhance its applicability in the treatment of childhood leukemia.
We tested ASNase wild-type (ASNase<sup>WT</sup>) and its glutaminase-deficient Q59L mutant (ASNase<sup>Q59L</sup>) and found that ASNase glutaminase activity contributed to durable anticancer activity against xenografts of the ASNS-negative Sup-B15 leukemia cell line in NOD/SCID gamma mice, whereas asparaginase activity alone yielded a mere growth delay.
Inhibition of autophagy by hydroxychloroquine, a well-tolerated autophagy inhibitor, reduced cell viability in both ETV6-RUNX1-positive cell lines and primary acute lymphoblastic leukemia samples, and selectively sensitized primary ETV6-RUNX1-positive leukemia samples to L asparaginase.
Similar to glutamine starvation, inhibition of glutamine metabolism with a chemical inhibitor currently under clinical evaluation was synthetically lethal with chloroquine and L-asparaginase, drugs approved for the treatment of malaria and leukemia, respectively.
In addition, L-asparaginase (used for the treatment of Leukemia and for acrylamide reduction in food industries) and cellulase (useful for biofuel production and other industrial applications) have been identified for the first time in this species, giving new insights into possible biotechnological applications of dinoflagellates.
The expression was compared between different types of leukemia and was studied in relation with clinical risk indicators and in vitro cytotoxicity of the MDR-related drugs daunorubicin (DNR), vincristine (VCR), and etoposide (VP16) and the non-MDR-related drugs prednisolone (PRD) and L-asparaginase (ASP).