Molecular mechanisms contributing to glucocorticoid resistance in lymphoid malignancies

Abstract

Despite the introduction of many novel therapies into the clinic to target hematological malignancies, glucocorticoids (GCs) still remain one of the cornerstone drugs in first-line treatment of lymphoid tumors. However, a significant portion of the patients display acquired GC therapy resistance. This review will describe the different molecular mechanisms that contribute to GC resistance in lymphoid tumors. These include suppression of glucocorticoid receptor (GR) expression, activation of cell signaling pathways that modulate GR function, differential recruitment of transcriptional co-regulators, and changes in chromatin accessibility. Many of these mechanisms are interconnected to genetic alterations associated with relapsed disease in lymphoid malignancies.

Keywords

Glucocorticoid receptor / therapy resistance / acute lymphoblastic leukemia / non-Hodgkin lymphoma / multiple myeloma

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