Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets

Pier Paolo Piccaluga, Claudio Agostinelli, Andrea Califano, Maura Rossi, Katia Basso, Simonetta Zupo, Philip Went, Ulf Klein, Pier Luigi Zinzani, Michele Baccarani, Riccardo Dalla Favera, Stefano A. Pileri

Research output: Contribution to journalArticle

205 Citations (Scopus)

Abstract

Peripheral T cell lymphoma, unspecified (PTCL/U), the most common form of PTCL, displays heterogeneous morphology and phenotype, poor response to treatment, and poor 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. PTCLs/U aberrantly express, among others, PDGFRα, a tyrosine-kinase receptor, whose deregulation is often related to a malignant phenotype. Notably, both phosphorylation of PDGFRα and sensitivity of cultured PTCL cells to imatinib (as well as to an inhibitor of histone deacetylase) were found. These results, which might be extended to other more rare PTCL categories, provide insight into tumor pathogenesis and clinical management of PTCL/U.

Original languageEnglish
Pages (from-to)823-834
Number of pages12
JournalJournal of Clinical Investigation
Volume117
Issue number3
DOIs
Publication statusPublished - Mar 1 2007

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Peripheral T-Cell Lymphoma
T-Lymphocytes
Gene Expression
HLA-DR Antigens
Transcriptome
Immunohistochemistry
Cell-Matrix Junctions
Phenotype
Histone Deacetylase Inhibitors
Receptor Protein-Tyrosine Kinases
Therapeutics
Cultured Cells
Carcinogenesis
Phosphorylation
Apoptosis
Genes
Neoplasms

ASJC Scopus subject areas

  • Medicine(all)

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Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets. / Piccaluga, Pier Paolo; Agostinelli, Claudio; Califano, Andrea; Rossi, Maura; Basso, Katia; Zupo, Simonetta; Went, Philip; Klein, Ulf; Zinzani, Pier Luigi; Baccarani, Michele; Favera, Riccardo Dalla; Pileri, Stefano A.

In: Journal of Clinical Investigation, Vol. 117, No. 3, 01.03.2007, p. 823-834.

Research output: Contribution to journalArticle

Piccaluga, PP, Agostinelli, C, Califano, A, Rossi, M, Basso, K, Zupo, S, Went, P, Klein, U, Zinzani, PL, Baccarani, M, Favera, RD & Pileri, SA 2007, 'Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets', Journal of Clinical Investigation, vol. 117, no. 3, pp. 823-834. https://doi.org/10.1172/JCI26833
Piccaluga, Pier Paolo ; Agostinelli, Claudio ; Califano, Andrea ; Rossi, Maura ; Basso, Katia ; Zupo, Simonetta ; Went, Philip ; Klein, Ulf ; Zinzani, Pier Luigi ; Baccarani, Michele ; Favera, Riccardo Dalla ; Pileri, Stefano A. / Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets. In: Journal of Clinical Investigation. 2007 ; Vol. 117, No. 3. pp. 823-834.
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