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.
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.affiliation: Department of Pathology, Centre Hospitalo-Universitaire Sart-Tilman, Tour de Pathologie +1, University of Liège, 4000 Liège, Belgium. l.deleval@ulg.ac.be
authors.forename: Laurence
authors.initials: L
authors.lastname: de Leval
authors.forename: David S
authors.initials: DS
authors.lastname: Rickman
authors.forename: Caroline
authors.initials: C
authors.lastname: Thielen
authors.forename: Aurélien de
authors.initials: Ad
authors.lastname: Reynies
authors.forename: Yen-Lin
authors.initials: YL
authors.lastname: Huang
authors.forename: Georges
authors.initials: G
authors.lastname: Delsol
authors.forename: Laurence
authors.initials: L
authors.lastname: Lamant
authors.forename: Karen
authors.initials: K
authors.lastname: Leroy
authors.forename: Josette
authors.initials: J
authors.lastname: Brière
authors.forename: Thierry
authors.initials: T
authors.lastname: Molina
authors.forename: Françoise
authors.initials: F
authors.lastname: Berger
authors.forename: Christian
authors.initials: C
authors.lastname: Gisselbrecht
authors.forename: Luc
authors.initials: L
authors.lastname: Xerri
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaulard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017730:Ki-1 Antigen / Q000096:biosynthesis; D016411:Lymphoma, T-Cell, Peripheral / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis
chemical_list: D017730:Ki-1 Antigen; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7