Blood, 2012-06, Vol.119 (24), p.5795-5806
2012
Details
- Autor(en) / Beteiligte
- Titel
- Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets
- Ist Teil von
- Blood, 2012-06, Vol.119 (24), p.5795-5806
- Ort / Verlag
- Washington, DC: Elsevier Inc
- Erscheinungsjahr
- 2012
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0006-4971eISSN: 1528-0020DOI: 10.1182/blood-2011-12-396150Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3779008
- Format
- –
- Schlagworte
- Adult, Aged, Base Sequence, Biological and medical sciences, Biomarkers, Tumor - genetics, Biomarkers, Tumor - metabolism, Cell Lineage - genetics, Chromosome Aberrations, Cluster Analysis, Crystallins - metabolism, Drug Resistance, Neoplasm - genetics, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genes, Neoplasm - genetics, Hematologic and hematopoietic diseases, Hematology, Human health and pathology, Humans, Intracellular Signaling Peptides and Proteins - antagonists & inhibitors, Intracellular Signaling Peptides and Proteins - metabolism, Isochromosomes - genetics, Life Sciences, Liver Neoplasms - drug therapy, Liver Neoplasms - genetics, Liver Neoplasms - pathology, Lymphoma, T-Cell - drug therapy, Lymphoma, T-Cell - genetics, Lymphoma, T-Cell - pathology, Male, Medical sciences, 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, Splenic Neoplasms - pathology, Syk Kinase, Young Adult