Notch Signaling Promotes Mature T-Cell Lymphomagenesis

Xin Gao, Chenguang Wang, Suhaib Abdelrahman, Nermin Kady, Carlos Murga-Zamalloa, Peter Gann, Maria Sverdlov, Ashley Wolfe, Avery Polk, Noah Brown, Nathanael G. Bailey, Kedar Inamdar, Sandro Casavilca-Zambrano, Jaime Montes, Carlos Barrionuevo, Luis Taxa, John Reneau, Christian W. Siebel, Ivan Maillard, Ryan A. Wilcox

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Peripheral T-cell lymphomas (PTCL) are agressive lymphomas engineered mouse models and spontaneous PTCL models were that develop from mature T cells. The most common PTCLs are used to functionally examine the role of Notch signaling, and genetically, molecularly, and clinically diverse and are generally Notch1/Notch2 blockade and pan-Notch blockade using domiassociated with dismal outcomes. While Notch signaling plays a nant-negative MAML significantly impaired the proliferation of critically important role in both the development of immature T malignant T cells and PTCL progression in these models. Treatment cells and their malignant transformation, its role in PTCL is poorly with DLL1/DLL4 blocking antibodies established that Notch sigunderstood, despite the increasingly appreciated function of Notch naling is ligand-dependent. Together, these findings reveal a role for in regulating the proliferation and differentiation of mature T cells. ligand-dependent Notch signaling in driving peripheral T-cell Here, we demonstrate that Notch receptors and their Delta-like lymphomagenesis. family ligands (DLL1/DLL4) play a pathogenic role in PTCL. Notch1 activation was observed in common PTCL subtypes, includSignificance: This work demonstrates that ligand-dependent ing PTCL-not otherwise specified (NOS). In a large cohort of PTCL-Notch activation promotes the growth and proliferation of mature NOS biopsies, Notch1 activation was significantly associated with T-cell lymphomas, providing new therapeutic strategies for this surrogate markers of proliferation. Complementary genetically group of aggressive lymphomas.

Original languageEnglish
Pages (from-to)3763-3773
Number of pages11
JournalCancer Research
Volume82
Issue number20
DOIs
StatePublished - 15 Oct 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
2022 American Association for Cancer Research.

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