Emerging Epigenetic and Posttranslational Mechanisms Controlling Resistance to Glucocorticoids in Acute Lymphoblastic Leukemia

Author:

Borin Cristina123,Pieters Tim123,Serafin Valentina4,Ntziachristos Panagiotis123

Affiliation:

1. Department of Biomolecular Medicine, Ghent University, Belgium

2. Center for Medical Genetics, Ghent University and University Hospital, Belgium

3. Cancer Research Institute Ghent (CRIG), Belgium

4. Department of Surgery Oncology and Gastroenterology, Oncology and Immunology Section, University of Padova, Italy

Abstract

Glucocorticoids are extensively used for the treatment of acute lymphoblastic leukemia as they pressure cancer cells to undergo apoptosis. Nevertheless, glucocorticoid partners, modifications, and mechanisms of action are hitherto poorly characterized. This hampers our understanding of therapy resistance, frequently occurring in leukemia despite the current therapeutic combinations using glucocorticoids in acute lymphoblastic leukemia. In this review, we initially cover the traditional view of glucocorticoid resistance and ways of targeting this resistance. We discuss recent progress in our understanding of chromatin and posttranslational properties of the glucocorticoid receptor that might be proven beneficial in our efforts to understand and target therapy resistance. We discuss emerging roles of pathways and proteins such as the lymphocyte-specific kinase that antagonizes glucocorticoid receptor activation and nuclear translocation. In addition, we provide an overview of ongoing therapeutic approaches that sensitize cells to glucocorticoids including small molecule inhibitors and proteolysis-targeting chimeras.

Publisher

Wiley

Subject

Hematology

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