Targeting steroid resistance in T-cell acute lymphoblastic leukemia. (November 2019)

• Record Type: Journal Article
• Authors: De Smedt, Renate; Morscio, Julie; Goossens, Steven; Van Vlierberghe, Pieter
• Is Part Of: Blood reviews. Volume 38(2019)
• Publication Date: 2019-11
• Subjects: T-cell acute lymphoblastic leukemia (T-ALL) -- Steroid resistance -- Relapse -- Signaling pathways; Hematology -- Periodicals; Hematology -- Periodicals; Hématologie -- Périodiques; Hematology; Electronic journals; Periodicals; 616.15
• DOI: 10.1016/j.blre.2019.100591
• Languages: English
• ISSNs: 0268-960X

Abstract

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.