Individuals with chronic myeloid leukemia (CML) are first treated with a drug known as imatinib mesylate. Although very effective, as the disease progresses it often becomes resistant to the drug. However, a team of researchers, at the University of Leicester, United Kingdom, and Thomas Jefferson University, Philadelphia, has identified a class of drugs that might enhance the therapeutic effects of imatinib mesylate and other drugs that target the same molecule.
The team, led by Paolo Salomoni and Bruno Calabretta, observed that for several different CML cell lines and primary cells, although imatinib mesylate killed the majority of cells, a marked proportion underwent a process known as autophagy. Consistent with studies indicating that the induction of autophagy can provide a mechanism of cellular survival, suppression of autophagy using either drugs or RNA interference enhanced imatinib mesylate–induced death of CML cell lines, primary CML cells, and CML stem cells. The authors therefore suggest that inhibitors of autophagy might be used with imatinib mesylate or other drugs that target the same molecule to enhance their therapeutic benefits.
AUTHOR CONTACT:
Paolo Salomoni
University of Leicester, Leicester, United Kingdom.
Phone: 44-116-2525568; Fax: 44-116-2525616; E-mail: ps90@le.ac.uk.
Bruno Calabretta
Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Phone: (215) 503-4522; Fax: (215) 923-0249; E-mail: bruno.calabretta@mail.jci.tju.edu.
View the PDF of this article at: https://www.the-jci.org/article.php?id=35660
Journal
Journal of Clinical Investigation