Induction of autophagy by imatinib sequesters Bcr‐Abl in autophagosomes and down‐regulates Bcr‐Abl protein

In this study, we show that following Imatinib treatment, Bcr‐Abl is sequestered into vesicular structures that co‐localize with the autophagy marker LC3 or GABARAP. This association is inhibited by siRNA mediated knockdown of autophagy regulators (Beclin 1/ATG7). Pharmacological inhibition of autophagy also reduced Bcr‐Abl/LC3 co‐localization in both K562 and CML patient cells. Bcr‐Abl protein expression was reduced with Imatinib treatment. Inhibition of both autophagy and proteasome activity in Imatinib treated cells was required to restore Bcr‐Abl protein levels to those of untreated cells. This ability to down‐regulate Bcr‐Abl protein levels through the induction of autophagy may be an additional and important feature of the activity of Imatinib. Am. J. Hematol., 2013. © 2013 Wiley Periodicals, Inc.

Source: American Journal of Hematology - February 26, 2013 Category: Hematology Authors: Baukje M. Elzinga, Michelle J. Nyhan, Lisa C. Crowley, Tracey R. O'Donovan, Mary R. Cahill, Sharon L. McKenna Tags: Research Article Source Type: research