Journal
BLOOD REVIEWS
Volume 38, Issue -, Pages -Publisher
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.blre.2019.100591
Keywords
T-cell acute lymphoblastic leukemia (T-ALL); Steroid resistance; Relapse; Signaling pathways
Categories
Funding
- Research Foundation Flanders
- European Hematology Association (EHA)
- Stand up to Cancer (the Flemish cancer society)
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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.
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