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Gene expression analysis of Peripheral T-cell Lymphoma/Unspecified

ABSTRACT: Peripheral T-cell lymphoma unspecified (PTCL/U), the most common form of PTCL, displays heterogeneous morphology and phenotype, poor response to treatment, and dismal prognosis. We demonstrate that PTCL/U shows a gene expression profile clearly distinct from that of normal T-cells. Comparison with the profiles of purified T-cell subpopulations [CD4+, CD8+, resting (HLA-DR-), and activated (HLA-DR+)] reveals that PTCLs/U are most closely related to activated peripheral T-lymphocytes, either CD4+ or CD8+. Interestingly, the global gene expression profile cannot be surrogated by routine CD4/CD8 immunohistochemistry. When compared with normal T-cells, PTCLs/U display deregulation of functional programs often involved in tumorigenesis (e.g. apoptosis, proliferation, cell adhesion, and matrix remodeling). Products of deregulated genes can be detected in PTCLs/U by immunohistochemistry with an ectopic, paraphysiologic or stromal location. Among others, PTCLs/U aberrantly express PDGFRA, a tyrosine-kinase receptor, whose deregulation is often related to a malignant phenotype. Notably, both phosphorylation of PDGFRA and sensitivity of cultured PTCL cells to imatinib (as well as to an inhibitor of histone-deacetylase) are found. These results, which might be extended to other rarer PTCL categories, are provided with implications for tumor pathogenesis and clinical management. Keywords: Molecular pathogenesis, molecular classification

ORGANISM(S): Homo sapiens

PROVIDER: GSE6338 | GEO | 2006/12/25

SECONDARY ACCESSION(S): PRJNA99639

REPOSITORIES: GEO

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Transcription profiling of human peripheral T-cell Lymphoma/Unspecified T cells and normal T cells

Project description:Peripheral T-cell lymphoma unspecified (PTCL/U), the most common form of PTCL, displays heterogeneous morphology and phenotype, poor response to treatment, and dismal prognosis. We demonstrate that PTCL/U shows a gene expression profile clearly distinct from that of normal T-cells. Comparison with the profiles of purified T-cell subpopulations [CD4+, CD8+, resting (HLA-DR-), and activated (HLA-DR+)] reveals that PTCLs/U are most closely related to activated peripheral T-lymphocytes, either CD4+ or CD8+. Interestingly, the global gene expression profile cannot be surrogated by routine CD4/CD8 immunohistochemistry. When compared with normal T-cells, PTCLs/U display deregulation of functional programs often involved in tumorigenesis (e.g. apoptosis, proliferation, cell adhesion, and matrix remodeling). Products of deregulated genes can be detected in PTCLs/U by immunohistochemistry with an ectopic, paraphysiologic or stromal location. Among others, PTCLs/U aberrantly express PDGFRA, a tyrosine-kinase receptor, whose deregulation is often related to a malignant phenotype. Notably, both phosphorylation of PDGFRA and sensitivity of cultured PTCL cells to imatinib (as well as to an inhibitor of histone-deacetylase) are found. These results, which might be extended to other rarer PTCL categories, are provided with implications for tumor pathogenesis and clinical management. Experiment Overall Design: 40 cases of Peripheral T-cell lymphoma (PTCL) were analyzed, including 28 PTCL/unspecified, 6 angioimmunoblastic (AITL) and 6 anaplastic large cell lymphoma cases (ALCL). Frozen lymph-nodes collected at diagnosis (before therapy) were used. In addition, 20 samples of normal T-cells (5 CD4+, 5 CD8+, 5 HLA-DR+, and 5 HLA-DR-) collected from peripheral blood and tonsils of healthy donors were studied. The HG U133 2.0 plus microarray (Affymetrix) was adopted.

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