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Regulation of glucocorticoid receptor steroid binding and trafficking by the hsp90/hsp70-based chaperone machinery: implications for clinical intervention

Leukemia volume 19, pages 710–712 (2005)Cite this article

This invited commentary is addressed in the paper by Tissing et al published in this issue of Leukemia.1 In this paper, the authors build upon previous studies2 showing hsp90 transcription is not related to glucocorticoid (GC) resistance in pediatric acute lymphoblastic leukemia (ALL). The authors postulate that GC resistance in pediatric ALL may result from altered expression of hsp90 per se, or from altered expression of a critical component of the hsp90/hsp70-based chaperone machinery that is involved in GC receptor (GR) maturation and nuclear translocation. The authors measure the transcripts from cells of matched GC-sensitive and GC-resistant patients, and further identify that the mRNA expression levels of hsp90 and hsp90/hsp70-based chaperone machinery co-chaperones are not correlated to GC resistance. Understanding the molecular mechanisms related to GC sensitivity/resistance in pediatric ALL is important for increasing treatment success for poor responders. The authors' findings are of further interest given that hsp90 inhibitors are being evaluated in clinical trials as antineoplastic agents in multiple cancer types including pediatric ALL, adult ALL, and chronic myelogenous leukemia.

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  1. Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, MI, USA

    P J M Murphy

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Murphy, P. Regulation of glucocorticoid receptor steroid binding and trafficking by the hsp90/hsp70-based chaperone machinery: implications for clinical intervention. Leukemia 19, 710–712 (2005). https://doi.org/10.1038/sj.leu.2403687

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