Title | The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | de Leval L, Rickman DS, Thielen C, de Reynies A, Huang Y-L, Delsol G, Lamant L, Leroy K, Brière J, Molina T, Berger F, Gisselbrecht C, Xerri L, Gaulard P |
Journal | Blood |
Volume | 109 |
Issue | 11 |
Pagination | 4952-63 |
Date Published | 2007 Jun 01 |
ISSN | 0006-4971 |
Keywords | Adult, Aged, Aged, 80 and over, Cluster Analysis, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Humans, Immunohistochemistry, Ki-1 Antigen, Lymphoma, T-Cell, Peripheral, Male, Middle Aged, Models, Genetic, Tumor Necrosis Factor Receptor Superfamily, Member 7 |
Abstract | The molecular alterations underlying the pathogenesis of angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma, unspecified (PTCL-u) are largely unknown. In order to characterize the ontogeny and molecular differences between both entities, a series of AITLs (n = 18) and PTCLs-u (n = 16) was analyzed using gene expression profiling. Unsupervised clustering correlated with the pathological classification and with CD30 expression in PTCL-u. The molecular profile of AITLs was characterized by a strong microenvironment imprint (overexpression of B-cell- and follicular dendritic cell-related genes, chemokines, and genes related to extracellular matrix and vascular biology), and overexpression of several genes characteristic of normal follicular helper T (T(FH)) cells (CXCL13, BCL6, PDCD1, CD40L, NFATC1). By gene set enrichment analysis, the AITL molecular signature was significantly enriched in published T(FH)-specific genes. The enrichment was higher for sorted AITL cells than for tissue samples. Overexpression of several T(FH) genes was validated by immunohistochemistry in AITLs. A few cases with molecular T(FH)-like features were identified among CD30(-) PTCLs-u. Our findings strongly support that T(FH) cells represent the normal counterpart of AITL, and suggest that the AITL spectrum may be wider than suspected, as a subset of CD30(-) PTCLs-u may derive from or be related to AITL. |
DOI | 10.1182/blood-2006-10-055145 |
Alternate Journal | Blood |
PubMed ID | 17284527 |
Related Lab:
Related Faculty:
David Rickman, Ph.D.