Modulation of Navitoclax Sensitivity by Dihydroartemisinin-Mediated MCL-1 Repression in BCR-ABL⁺ B-Lineage Acute Lymphoblastic Leukemia.

ABSTRACT: Purpose: BCR-ABL⁺ B-ALL leukemic cells are highly dependent on the expression of endogenous antiapoptotic MCL-1 to promote viability and are resistant to BH3-mimetic agents such as navitoclax (ABT-263) that target BCL-2, BCL-X_L, and BCL-W. However, the survival of most normal blood cells and other cell types is also dependent on Mcl-1 Despite the requirement for MCL-1 in these cell types, initial reports of MCL-1-specific BH3-mimetics have not described any overt toxicities associated with single-agent use, but these agents are still early in clinical development. Therefore, we sought to identify approved drugs that could sensitize leukemic cells to ABT-263.Experimental Design: A screen identified dihydroartemisinin (DHA), a water-soluble metaboli

SUBMITTER: Budhraja A 

PROVIDER: S-EPMC5786379 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature