Investigating and targeting chronic lymphocytic leukemia metabolism with the human immunodeficiency virus protease inhibitor ritonavir and metformin.

ABSTRACT: Chronic lymphocytic leukemia (CLL) remains fatal due to the development of resistance to existing therapies. Targeting abnormal glucose metabolism sensitizes various cancer cells to chemotherapy and/or elicits toxicity. Examination of glucose dependency in CLL demonstrated variable sensitivity to glucose deprivation. Further evaluation of metabolic dependencies of CLL cells resistant to glucose deprivation revealed increased engagement of fatty acid oxidation upon glucose withdrawal. Investigation of glucose transporter expression in CLL reveals up-regulation of glucose transporter GLUT4. Treatment of CLL cells with human immunodeficiency (HIV) protease inhibitor ritonavir, which inhibits GLUT4, elicits toxicity similar to that elicited upon glucose deprivation. CLL cells resistant to rito

SUBMITTER: Adekola KU 

PROVIDER: S-EPMC4868500 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature