Celastrol, a novel HSP90 inhibitor, depletes Bcr-Abl and induces apoptosis in imatinib-resistant chronic myelogenous leukemia cells harboring T315I mutation

T315I Bcr-Abl in chronic myelogenous leukemia (CML) is the most notorious point mutations to elicit acquired resistance to imatinib. In the present study, we investigated the effect of celastrol on CML cells bearing wild-type Bcr-Abl or T315I-mutant. The results revealed that celastrol potently downregulated the protein levels of Bcr-Abl, and inhibited the growth in CML cells in vitro and in nude mouse xenografts regardless of Bcr-Abl mutation status. Celastrol induced mitochondrial-dependent apoptosis. In conclusion, celastrol exhibits potent activity against CML cells bearing wild-type Bcr-Abl or -the T315I-mutant. (C) 2009 Elsevier Ireland Ltd. All rights reserved.