Gene expression analysis of peripheral T cell lymphoma, unspecified, reveals distinct profiles and new potential therapeutic targets.
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, PDGFRalpha, a tyrosine-kinase receptor, whose deregulation is often related to a malignant phenotype. Notably, both phosphorylation of PDGFRalpha 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.
Piccaluga
Pier Paolo
PP
Institute of Hematology and Medical Oncology L. and A. Seràgnoli, Sant'Orsola-Malpighi Hospital, University of Bologna, Bologna, Italy.
Agostinelli
Claudio
C
Califano
Andrea
A
Rossi
Maura
M
Basso
Katia
K
Zupo
Simonetta
S
Went
Philip
P
Klein
Ulf
U
Zinzani
Pier Luigi
PL
Baccarani
Michele
M
Dalla Favera
Riccardo
R
Pileri
Stefano A
SA
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002448:Cell Adhesion / Q000235:genetics; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006684:HLA-DR Antigens / Q000032:analysis; D006801:Humans; D008213:Lymphocyte Activation; D016411:Lymphoma, T-Cell, Peripheral / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis
D006684:HLA-DR Antigens