Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets.

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Date

2012

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Périmètre
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Serveur académique Lausannois

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Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.1182/blood-2011-12-396150

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/22510872

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1528-0020

Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_E4B1C2D974C93

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Serveur Académique Lausannois

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Université de Lausanne et CHUV

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info:eu-repo/semantics/openAccess , Copying allowed only for non-profit organizations , https://serval.unil.ch/disclaimer

Mots-clés 0

Adult; Aged; Base Sequence; Cell Lineage/genetics; Chromosome Aberrations; Cluster Analysis; Crystallins/metabolism; Drug Resistance, Neoplasm/genetics; Female; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Genes, Neoplasm/genetics; Humans; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors; Intracellular Signaling Peptides and Proteins/metabolism; Isochromosomes/genetics; Liver Neoplasms/drug therapy; Liver Neoplasms/genetics; Lymphoma, T-Cell/drug therapy; Lymphoma, T-Cell/genetics; Male; Membrane Proteins/metabolism; Middle Aged; Molecular Sequence Data; Molecular Targeted Therapy; Protein-Tyrosine Kinases/antagonists & inhibitors; Protein-Tyrosine Kinases/metabolism; Receptors, Antigen, T-Cell, alpha-beta/genetics; Receptors, Antigen, T-Cell, gamma-delta/genetics; Splenic Neoplasms/drug therapy; Splenic Neoplasms/genetics; Tumor Markers, Biological/genetics; Tumor Markers, Biological/metabolism; Young Adult

Sujets proches En

Lymphoma Non-Hodgkin's lymphoma Germinoblastomas Sarcoma, Germinoblastic Sarcoma, Immunoblastic Reticulolymphosarcomas Immunoblastomas

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M. Travert et al., « Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets. », Serveur académique Lausannois, ID : 10.1182/blood-2011-12-396150

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The pathogenesis of hepatosplenic T-cell lymphoma (HSTL), a rare entity mostly derived from γδ T cells and usually with a fatal outcome, remains largely unknown. In this study, HSTL samples (7γδ and 2αβ) and the DERL2 HSTL cell line were subjected to combined gene-expression profiling and array-based comparative genomic hybridization. Compared with other T-cell lymphomas, HSTL had a distinct molecular signature irrespective of TCR cell lineage. Compared with peripheral T-cell lymphoma, not otherwise specified and normal γδ T cells, HSTL overexpressed genes encoding NK-cell-associated molecules, oncogenes (FOS and VAV3), the sphingosine-1-phosphatase receptor 5 involved in cell trafficking, and the tyrosine kinase SYK, whereas the tumor-suppressor gene AIM1 (absent in melanoma 1) was among the most down-expressed. We found highly methylated CpG islands of AIM1 in DERL2 cells, and decitabine treatment induced a significant increase in AIM1 transcripts. Syk was present in HSTL cells and DERL2 cells contained phosphorylated Syk and were sensitive to a Syk inhibitor in vitro. Genomic profiles confirmed recurrent isochromosome 7q (n = 6/9) without alterations at the SYK and AIM1 loci. Our results identify a distinct molecular signature for HSTL and highlight oncogenic pathways that offer rationale for exploring new therapeutic options such as Syk inhibitors and demethylating agents.

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