Targeting steroid resistance in T-cell acute lymphoblastic leukemia.

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is characterized by a variable response to steroids during induction and/or consolidation therapy. Notably, recent work suggested that these differences in glucocorticoid sensitivity might, at least in part, be mediated by hyperactivation of specific oncogenic pathways such as RAS/MEK/ERK, PI3K/AKT and IL7R/JAK/STAT. In this review, we elaborate on putative associations between aberrant signaling, therapy resistance, incidence of relapse and clinical outcome in human T-ALL. Furthermore, we emphasize that this potential association with clinical parameters might also be mediated by the tumor microenvironment as a result of increased sensitivity of leukemic T-cells towards cytokine induced signaling pathway activation. With this in mind, we provide an overview of small molecule inhibitors that might have clinical potential for the treatment of human T-ALL in the near future as a result of their ability to overcome steroid resistance thereby potentially increasing survival rates in this aggressive hematological neoplasm.

• Authors: Renate De Smedt, Julie Morscio, Steven Goossens, Pieter Van Vlierberghe
• Journal: Blood reviews (Blood Rev) Vol. 38 Pg. 100591 (11 2019) ISSN: 1532-1681 [Electronic] England
• PMID: 31353059 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2019 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• Glucocorticoids
• Small Molecule Libraries

Topics

• Animals
• Antineoplastic Agents (pharmacology, therapeutic use)
• Drug Discovery (methods)
• Drug Resistance (drug effects)
• Glucocorticoids (pharmacology, therapeutic use)
• Humans
• Molecular Targeted Therapy
• Precursor T-Cell Lymphoblastic Leukemia-Lymphoma (drug therapy, metabolism)
• Signal Transduction (drug effects)
• Small Molecule Libraries (pharmacology, therapeutic use)