Document Detail


Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets.
MedLine Citation:
PMID:  22510872     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Marion Travert; Yenlin Huang; Laurence de Leval; Nadine Martin-Garcia; Marie-Helene Delfau-Larue; Françoise Berger; Jacques Bosq; Josette Brière; Jean Soulier; Elizabeth Macintyre; Teresa Marafioti; Aurélien de Reyniès; Philippe Gaulard
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-04-17
Journal Detail:
Title:  Blood     Volume:  119     ISSN:  1528-0020     ISO Abbreviation:  Blood     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-15     Completed Date:  2012-08-24     Revised Date:  2013-09-24    
Medline Journal Info:
Nlm Unique ID:  7603509     Medline TA:  Blood     Country:  United States    
Other Details:
Languages:  eng     Pagination:  5795-806     Citation Subset:  AIM; IM    
Affiliation:
Inserm U955, Créteil, France.
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MeSH Terms
Descriptor/Qualifier:
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,  metabolism
Isochromosomes / genetics
Liver Neoplasms / drug therapy*,  genetics*,  pathology
Lymphoma, T-Cell / drug therapy*,  genetics*,  pathology
Male
Membrane Proteins / metabolism
Middle Aged
Molecular Sequence Data
Molecular Targeted Therapy*
Protein-Tyrosine Kinases / antagonists & inhibitors,  metabolism
Receptors, Antigen, T-Cell, alpha-beta / genetics
Receptors, Antigen, T-Cell, gamma-delta / genetics
Splenic Neoplasms / drug therapy*,  genetics*,  pathology
Tumor Markers, Biological / genetics,  metabolism
Young Adult
Chemical
Reg. No./Substance:
0/AIM1 protein, human; 0/Crystallins; 0/Intracellular Signaling Peptides and Proteins; 0/Membrane Proteins; 0/Receptors, Antigen, T-Cell, alpha-beta; 0/Receptors, Antigen, T-Cell, gamma-delta; 0/Tumor Markers, Biological; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.1/Syk kinase
Comments/Corrections

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