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.
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.
de Leval
Laurence
L
Department of Pathology, Centre Hospitalo-Universitaire Sart-Tilman, Tour de Pathologie +1, University of Liège, 4000 Liège, Belgium. l.deleval@ulg.ac.be
Rickman
David S
DS
Thielen
Caroline
C
Reynies
Aurélien de
Ad
Huang
Yen-Lin
YL
Delsol
Georges
G
Lamant
Laurence
L
Leroy
Karen
K
Brière
Josette
J
Molina
Thierry
T
Berger
Françoise
F
Gisselbrecht
Christian
C
Xerri
Luc
L
Gaulard
Philippe
P
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
D017730:Ki-1 Antigen; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7