Restored biosynthetic pathways induced by MSCs serve as rescue mechanism in leukemia cells after L-asparaginase therapy
Abstract
L-asparaginase (ASNase), the drug included on the World Health Organization's List of Essential
Medicines, is irreplaceable in the front-line treatment of childhood acute lymphoblastic leukemia
(ALL)1 . However, the relapse of ALL is often associated with resistance to ASNase and its mechanisms are not fully understood. The cytotoxic effect of ASNase relies on depleting exogenous asparagine (Asn) and glutamine (Gln), inducing apoptosis in leukemic cells because of their reduced capability of Asn synthesis. Our previous in vitro data demonstrated that ASNase triggers metabolic reprogramming of leukemic cells which impedes the anti-leukemic effect. Metabolic processes of leukemic cells have been shown to be altered by the environment of the bone marrow (BM) which may contribute to chemoresistance. Herein, we investigated the impact of BM attributes on cellular metabolic processes of leukemic cells in order to demonstrate the more complex picture of
ASNase-driven metabolic rewiring and its role in the mechanism of resistance.