HSP90 inhibition depletes DNA repair proteins to sensitize acute myelogenous leukemia to nucleoside analog chemotherapeutics.

The treatment of acute myelogenous leukemia (AML) relies heavily on cytarabine (Ara-C) containing chemotherapy. (b) Immunoblot analysis of Chk1, Rad51, and GAPDH (loading control) in AML blasts cells after exposure to a 0.25 µM onalespib for 24 or 36 h. (c) OCI-AML3 cells were left untreated (control) or exposed to 0.25 µM onalespib for 24 h before undergoing DNA damage with 2 Gy IR. However, cells exposed to the combination of onalespib and Ara-C strongly induce S-phase arrest which may explain the mechanism by which onalespib sensitizes OCI-AML3 cells to Ara-C. [Extracted from the article]