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

Cristina Borin1,2,3, Tim Pieters1,2,3, Valentina Serafin4

  • 1Department of Biomolecular Medicine, Ghent University, Belgium.

Hemasphere
|June 26, 2023
PubMed

Insights

Glucocorticoids treat acute lymphoblastic leukemia by inducing cancer cell death. Understanding glucocorticoid resistance mechanisms and receptor properties is key to improving leukemia therapy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Glucocorticoids are vital in treating acute lymphoblastic leukemia (ALL).
  • Therapy resistance to glucocorticoids is a significant clinical challenge in ALL.
  • The precise mechanisms and interacting partners of glucocorticoids in ALL remain incompletely understood.

Purpose of the Study:

  • To review current knowledge on glucocorticoid resistance in ALL.
  • To explore recent advancements in understanding glucocorticoid receptor (GR) function and modifications.
  • To discuss novel therapeutic strategies targeting glucocorticoid resistance.

Main Methods:

  • Literature review focusing on glucocorticoid action in ALL.
  • Analysis of recent findings on GR chromatin interactions and posttranslational modifications.
  • Examination of emerging pathways and proteins influencing GR activity, such as lymphocyte-specific kinase (LCK).

Main Results:

  • Traditional views on glucocorticoid resistance are presented alongside new targeting strategies.
  • Advances in understanding GR's chromatin and posttranslational states offer insights into resistance.
  • The role of LCK in antagonizing GR activation and nuclear translocation is highlighted.

Conclusions:

  • Improved understanding of GR biology is crucial for overcoming ALL therapy resistance.
  • Emerging therapeutic approaches, including small molecule inhibitors and proteolysis-targeting chimeras, show promise.
  • Targeting resistance mechanisms can enhance glucocorticoid efficacy in ALL treatment.

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