The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (T-FH) cells
de Leval, Laurence; Rickman, David; Thielen, Carolineet al.
[en] 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 TFH 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.
The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (T-FH) cells
Publication date :
01 June 2007
Journal title :
Blood
ISSN :
0006-4971
eISSN :
1528-0020
Publisher :
Amer Soc Hematology, Washington, United States - Washington
Volume :
109
Issue :
11
Pages :
4952-4963
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
Fondation contre le Cancer [BE] Fonds Léon Fredericq [BE] F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
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