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Tosello V, Ferrando AA. The NOTCH signaling pathway: role in the pathogenesis of T-cell acute lymphoblastic leukemia and implication for therapy. Ther Adv Hematol. 2013;4(3):199-210doi: 10.1177/2040620712471368.
Tosello, V., & Ferrando, A. A. (2013). The NOTCH signaling pathway: role in the pathogenesis of T-cell acute lymphoblastic leukemia and implication for therapy. Therapeutic advances in hematology, 4(3), 199-210. https://doi.org/10.1177/2040620712471368
Tosello, Valeria, and Ferrando, Adolfo A. "The NOTCH signaling pathway: role in the pathogenesis of T-cell acute lymphoblastic leukemia and implication for therapy." Therapeutic advances in hematology vol. 4,3 (2013): 199-210. doi: https://doi.org/10.1177/2040620712471368
Tosello V, Ferrando AA. The NOTCH signaling pathway: role in the pathogenesis of T-cell acute lymphoblastic leukemia and implication for therapy. Ther Adv Hematol. 2013 Jun;4(3):199-210. doi: 10.1177/2040620712471368. PMID: 23730497; PMCID: PMC3666445.
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Ther Adv Hematol. 2013 Jun;4(3):199-210. doi: 10.1177/2040620712471368.

The NOTCH signaling pathway: role in the pathogenesis of T-cell acute lymphoblastic leukemia and implication for therapy.

Therapeutic advances in hematology

Valeria Tosello, Adolfo A Ferrando

Affiliations

  1. Istituto Oncologico Veneto, IRCCS, Italy.

PMID: 23730497 PMCID: PMC3666445 DOI: 10.1177/2040620712471368

Abstract

T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is characterized by aberrant activation of NOTCH1 in over 60% of T-ALL cases. The high prevalence of activating NOTCH1 mutations highlights the critical role of NOTCH signaling in the pathogenesis of this disease and has prompted the development of therapeutic approaches targeting the NOTCH signaling pathway. Small molecule gamma secretase inhibitors (GSIs) can effectively inhibit oncogenic NOTCH1 and are in clinical testing for the treatment of T-ALL. Treatment with GSIs and glucocorticoids are strongly synergistic and may overcome the gastrointestinal toxicity associated with systemic inhibition of the NOTCH pathway. In addition, emerging new anti-NOTCH1 therapies include selective inhibition of NOTCH1 with anti-NOTCH1 antibodies and stapled peptides targeting the NOTCH transcriptional complex in the nucleus.

Keywords: NOTCH1; T-ALL; gamma-secretase inhibitor

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