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. Academic Article uri icon

Overview

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.

authors

  • de Leval, Laurence
  • Rickman, David S.
  • Thielen, Caroline
  • Reynies, Aurélien de
  • Huang, Yen-Lin
  • Delsol, Georges
  • Lamant, Laurence
  • Leroy, Karen
  • Brière, Josette
  • Molina, Thierry
  • Berger, Françoise
  • Gisselbrecht, Christian
  • Xerri, Luc
  • Gaulard, Philippe

publication date

  • February 6, 2007

Research

keywords

  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Lymphoma, T-Cell, Peripheral

Identity

Scopus Document Identifier

  • 34249652415

Digital Object Identifier (DOI)

  • 10.1182/blood-2006-10-055145

PubMed ID

  • 17284527

Additional Document Info

volume

  • 109

issue

  • 11