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Targeting steroid resistance in T-cell acute lymphoblastic leukemia

Renate De Smedt (UGent) , Julie Morscio (UGent) , Steven Goossens (UGent) and Pieter Van Vlierberghe (UGent)
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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.
Keywords
T-cell acute lymphoblastic leukemia (T-ALL), Steroid resistance, Relapse, Signaling pathways, OF-FUNCTION MUTATIONS, JAK/STAT PATHWAY INHIBITION, SMALL-MOLECULE INHIBITOR, PIM PROTEIN-KINASES, GLUCOCORTICOID RESISTANCE, ANTILEUKEMIC ACTIVITY, DUAL INHIBITION, PHOSPHATIDYLINOSITOL 3-KINASE, THERAPEUTIC STRATEGY, SIGNALING PATHWAYS

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MLA
De Smedt, Renate, et al. “Targeting Steroid Resistance in T-Cell Acute Lymphoblastic Leukemia.” BLOOD REVIEWS, vol. 38, 2019, doi:10.1016/j.blre.2019.100591.
APA
De Smedt, R., Morscio, J., Goossens, S., & Van Vlierberghe, P. (2019). Targeting steroid resistance in T-cell acute lymphoblastic leukemia. BLOOD REVIEWS, 38. https://doi.org/10.1016/j.blre.2019.100591
Chicago author-date
De Smedt, Renate, Julie Morscio, Steven Goossens, and Pieter Van Vlierberghe. 2019. “Targeting Steroid Resistance in T-Cell Acute Lymphoblastic Leukemia.” BLOOD REVIEWS 38. https://doi.org/10.1016/j.blre.2019.100591.
Chicago author-date (all authors)
De Smedt, Renate, Julie Morscio, Steven Goossens, and Pieter Van Vlierberghe. 2019. “Targeting Steroid Resistance in T-Cell Acute Lymphoblastic Leukemia.” BLOOD REVIEWS 38. doi:10.1016/j.blre.2019.100591.
Vancouver
1.
De Smedt R, Morscio J, Goossens S, Van Vlierberghe P. Targeting steroid resistance in T-cell acute lymphoblastic leukemia. BLOOD REVIEWS. 2019;38.
IEEE
[1]
R. De Smedt, J. Morscio, S. Goossens, and P. Van Vlierberghe, “Targeting steroid resistance in T-cell acute lymphoblastic leukemia,” BLOOD REVIEWS, vol. 38, 2019.
@article{8627033,
  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.}},
  articleno    = {{100591}},
  author       = {{De Smedt, Renate and Morscio, Julie and Goossens, Steven and Van Vlierberghe, Pieter}},
  issn         = {{0268-960X}},
  journal      = {{BLOOD REVIEWS}},
  keywords     = {{T-cell acute lymphoblastic leukemia (T-ALL),Steroid resistance,Relapse,Signaling pathways,OF-FUNCTION MUTATIONS,JAK/STAT PATHWAY INHIBITION,SMALL-MOLECULE INHIBITOR,PIM PROTEIN-KINASES,GLUCOCORTICOID RESISTANCE,ANTILEUKEMIC ACTIVITY,DUAL INHIBITION,PHOSPHATIDYLINOSITOL 3-KINASE,THERAPEUTIC STRATEGY,SIGNALING PATHWAYS}},
  language     = {{eng}},
  pages        = {{10}},
  title        = {{Targeting steroid resistance in T-cell acute lymphoblastic leukemia}},
  url          = {{http://dx.doi.org/10.1016/j.blre.2019.100591}},
  volume       = {{38}},
  year         = {{2019}},
}

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