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Current Topics in Steroid Research   Volumes    Volume 9 
Abstract
Advances in the understanding of the mechanisms of glucocorticoid sensitivity and resistance in lymphoid malignancies
Jack Zhuang, Andrew R. Pettitt
Pages: 93 - 109
Number of pages: 17
Current Topics in Steroid Research
Volume 9 

Copyright © 2012 Research Trends. All rights reserved

ABSTRACT
 
Glucocorticoids (GCs) represent an important component of treatment regimens for lymphoid malignancies including acute lymphoblastic leukaemia (ALL), multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL).  However, the exact mechanisms underlying their cytotoxicity are not well understood.  Nor is it understood why some patients respond to GC treatment while others do not. Understanding the molecular mechanisms underlying GC sensitivity and resistance is important as it could provide the basis for novel therapeutic strategies. It is noteworthy that, although the cytotoxic effects of glucocorticoids on cells of lymphocytic origin have been known for decades, it is only over the last 10-15 years that we have begun to understand the molecular mode of action of GCs in lymphoid malignancies. Research interest in the subject, and in particular the mechanisms underlying GC resistance, has been growing steadily over this period, and it is now clear that GC-induced killing requires transcriptional activity resulting in either the induction of death-inducing genes or the repression of survival genes. Whilst GC-induced transcriptional activity and associated de novo protein synthesis are critical events in determining the cellular response to GCs, emerging evidence suggests that post-translational modification of certain proteins can also influence GC sensitivity. Conversely, defects in the GC-initiated apoptotic signalling pathway can contribute to glucocorticoid resistance. In this review, we will discuss the molecular mechanisms underlying cellular responsiveness/resistance to glucocorticoid-induced cytotoxicity in lymphoid malignancies and highlight the similarities and differences between GC sensitivity/resistance in CLL, ALL and MM.
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