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    Wiskott-Aldrich syndrome protein (WASP) is a tumor suppressor in T cell lymphoma.

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    Authors
    Menotti, Matteo
    Ambrogio, C
    Cheong, TC
    Pighi, C
    Mota, I
    Cassel, SH
    Compagno, M
    Wang, Q
    Dall'Olio, R
    Minero, VG
    Poggio, T
    Sharma, GG
    Patrucco, E
    Mastini, C
    Choudhari, R
    Pich, A
    Zamo, A
    Piva, R
    Giliani, S
    Mologni, L
    Collings, CK
    Kadoch, C
    Gambacorti-Passerini, C
    Notarangelo, LD
    Anton, IM
    Voena, C
    Chiarle, R
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    Affiliation
    Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy
    Issue Date
    2018
    
    Metadata
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    Abstract
    In T lymphocytes, the Wiskott-Aldrich Syndrome protein (WASP) and WASP-interacting-protein (WIP) regulate T cell antigen receptor (TCR) signaling, but their role in lymphoma is largely unknown. Here we show that the expression of WASP and WIP is frequently low or absent in anaplastic large cell lymphoma (ALCL) compared to other T cell lymphomas. In anaplastic lymphoma kinase-positive (ALK+) ALCL, WASP and WIP expression is regulated by ALK oncogenic activity via its downstream mediators STAT3 and C/EBP-?. ALK+ lymphomas were accelerated in WASP- and WIP-deficient mice. In the absence of WASP, active GTP-bound CDC42 was increased and the genetic deletion of one CDC42 allele was sufficient to impair lymphoma growth. WASP-deficient lymphoma showed increased mitogen-activated protein kinase (MAPK) pathway activation that could be exploited as a therapeutic vulnerability. Our findings demonstrate that WASP and WIP are tumor suppressors in T cell lymphoma and suggest that MAP-kinase kinase (MEK) inhibitors combined with ALK inhibitors could achieve a more potent therapeutic effect in ALK+ ALCL.
    Citation
    Menotti M, Ambrogio C, Cheong TC, Pighi C, Mota I, Cassel SH, et al. Wiskott-Aldrich syndrome protein (WASP) is a tumor suppressor in T cell lymphoma. Nat Med. 2018 Dec 3.
    Journal
    Nature Medicine
    URI
    http://hdl.handle.net/10541/621473
    DOI
    10.1038/s41591-018-0262-9
    PubMed ID
    30510251
    Additional Links
    https://dx.doi.org/10.1038/s41591-018-0262-9
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41591-018-0262-9
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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