The Distinct Molecular Signature Of Hepatosplenic T-Cell Lymphoma (Hstl) Identifies Oncogenic Pathways With Potential Therapeutic Relevance

Détails

ID Serval
serval:BIB_50489C8363F8
Type
Actes de conférence (partie): contribution originale à la littérature scientifique, publiée à l'occasion de conférences scientifiques, dans un ouvrage de compte-rendu (proceedings), ou dans l'édition spéciale d'un journal reconnu (conference proceedings).
Sous-type
Abstract (résumé de présentation): article court qui reprend les éléments essentiels présentés à l'occasion d'une conférence scientifique dans un poster ou lors d'une intervention orale.
Collection
Publications
Institution
Titre
The Distinct Molecular Signature Of Hepatosplenic T-Cell Lymphoma (Hstl) Identifies Oncogenic Pathways With Potential Therapeutic Relevance
Titre de la conférence
11th International Conference on Malignant Lymphoma
Auteur(s)
Travert M., Huang Y., De Reynies A., De Leval L., Martin-Garcia N., Delfau-Larue M., Berger F., Briere J., Macintyre E., Marafioti T., Gaulard P.
Adresse
Lugano, Switzerland, Jun 15-18, 2011
ISBN
0923-7534
Statut éditorial
Publié
Date de publication
2011
Peer-reviewed
Oui
Volume
22
Série
Annals of Oncology
Pages
147
Langue
anglais
Notes
Publication type : Meeting Abstract
Résumé
Background: HSTL is a rare entity characterized by an infiltration of bone marrow, spleen and liver tissues by neoplastic gammadelta (gd) -more rarely alphabeta (ab)- T cells. Its pathogenesis is poorly understood. Our purpose was to identify the molecular signature of HSTL and explore molecular pathways implicated in its pathogenesis.Methods: Gene expression profiling and array CGH analysis of 10 HSTL samples (7gd, 3ab), 1 HSTL cell line (DERL2), 2 normal gd samples together with 16 peripheral T-cell lymphoma not otherwise specified (PTCL,NOS) and 7 nasal NK/T cell lymphomas were performed.Results: By unsupervised analysis, ab and gdHSTL clustered together remarkably separated from other lymphoma entities. Compared to PTCL, NOS, HSTL overexpresed genes encoding NK-associated molecules, oncogenes (VAV3) and the Sphingosine-1-phosphatase receptor 5 involved in cell trafficking. Compared to normal gd cells, HSTL overexpressed genes encoding NK-cell and multi drug resistance-associated molecules, transcription factors (RHOB), oncogenes (MAFB, FOS, JUN, VAV3) and the tyrosine kinase SYK whereas genes encoding cytotoxic molecules and the tumor suppressor gene AIM1 were among the most downregulated. By immunohistochemistry, SYK was demonstrated on HSTL cells with expression of its phosphorylated form in DERL2 cells by Western blot. Functional studies using a SYK inhibitor revealed a dose dependent increase of apoptotic DERL2 cells suggesting that SYK could be a candidate target for pharmacologic inhibition. Downexpression of AIM1 was validated by qRT-PCR. Methylation analysis of DERL2 genomic DNA treated by bisulfite demonstrated highly methylated CpG islands of AIM1. Genomic profiles confirmed recurrent isochromosome 7q (n=6/9) without alterations at 9q22 and 6q21 containing SYK and AIM1 genes, respectively.Conclusion: The current study identifies a distinct molecular signature for HSTL and highlights oncogenic pathways which offer rationale for exploring new therapeutic options such as SYK inhibitors. It supports the view of gd and ab HSTL as a single entity.
Mots-clé
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Web of science
Création de la notice
15/07/2011 11:43
Dernière modification de la notice
20/08/2019 15:06
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