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Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets.: Molecular Signature of Hepatosplenic T-cell Lymphoma

Abstract : 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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https://www.hal.inserm.fr/inserm-00730464
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Submitted on : Monday, October 1, 2012 - 7:00:52 AM
Last modification on : Wednesday, September 16, 2020 - 5:30:46 PM
Long-term archiving on: : Wednesday, January 2, 2013 - 3:15:13 AM

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Marion Travert, Yenlin Huang, Laurence de Leval, Nadine Martin-Garcia, Marie-Helene Delfau-Larue, et al.. Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets.: Molecular Signature of Hepatosplenic T-cell Lymphoma. Blood, American Society of Hematology, 2012, 119 (24), pp.5795-806. ⟨10.1182/blood-2011-12-396150⟩. ⟨inserm-00730464⟩

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