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Blood, 1 June 2007, Vol. 109, No. 11, pp. 4952-4963. Prepublished online as a Blood First Edition Paper on February 6, 2007; DOI 10.1182/blood-2006-10-055145. This Article Full Text Full Text (PDF) Supplemental Tables and Figure All Versions of this Article: blood-2006-10-055145v1 109/11/4952    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by de Leval, L. Articles by Gaulard, P. Search for Related Content PubMed PubMed Citation Articles by de Leval, L. Articles by Gaulard, P. Related Collections Neoplasia Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA 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 Laurence de Leval1, David S. Rickman2, Caroline Thielen1, Aurélien de Reynies2, Yen-Lin Huang3,5, Georges Delsol6, Laurence Lamant6, Karen Leroy3,4,5, Josette Brière7, Thierry Molina8, Françoise Berger9, Christian Gisselbrecht10, Luc Xerri11, and Philippe Gaulard3,4,5 1 Pathology, Centre Hospitalo-Universitaire (CHU) Sart-Tilman, University of Liège, Belgium; 2 Ligue Contre le Cancer, Paris, France; 3 Institut National de la Santé et de la Recherche Médicale (Inserm), Unité 617, Créteil, France; 4 Assistance Publique–Hôpitaux de Paris (AP-HP), Groupe hospitalier Henri Mondor, Département de Pathologie, Créteil, France; 5 Université Paris 12, Faculté de médecine, Institut Mondor de médecine moléculaire, Créteil, France; 6 Pathology, CHU Purpan, Toulouse, France; 7 Pathology, Hôpital Saint-Louis, Paris, France; 8 Pathology, Hôtel-Dieu, Paris, France; 9 Pathology, Centre Hospitalier Lyon Sud, Pierre Benite, France; 10 Hematology, Hôpital Saint-Louis, Paris, France; 11 Pathology, Institut Paoli Calmettes, Marseille, France 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 (TFH) cells (CXCL13, BCL6, PDCD1, CD40L, NFATC1). By gene set enrichment analysis, the AITL molecular signature was significantly enriched in published TFH-specific genes. The enrichment was higher for sorted AITL cells than for tissue samples. Overexpression of several TFH genes was validated by immunohistochemistry in AITLs. A few cases with molecular TFH-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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: B. Chetaille, F. Bertucci, P. Finetti, B. Esterni, A. Stamatoullas, J. M. Picquenot, M. C. Copin, F. Morschhauser, O. Casasnovas, T. Petrella, et al. Molecular profiling of classical Hodgkin lymphoma tissues uncovers variations in the tumor microenvironment and correlations with EBV infection and outcome Blood, March 19, 2009; 113(12): 2765 - 3775. [Abstract] [Full Text] [PDF] K. Miyazaki, M. Yamaguchi, H. Imai, T. Kobayashi, S. Tamaru, K. Nishii, M. Yuda, H. Shiku, and N. 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Gaulard Pathobiology and Molecular Profiling of Peripheral T-Cell Lymphomas Hematology, January 1, 2008; 2008(1): 272 - 279. [Abstract] [Full Text] [PDF] V. L. Bryant, C. S. Ma, D. T. Avery, Y. Li, K. L. Good, L. M. Corcoran, R. de Waal Malefyt, and S. G. Tangye Cytokine-Mediated Regulation of Human B Cell Differentiation into Ig-Secreting Cells: Predominant Role of IL-21 Produced by CXCR5+ T Follicular Helper Cells J. Immunol., December 15, 2007; 179(12): 8180 - 8190. [Abstract] [Full Text] [PDF] P. P. Piccaluga, C. Agostinelli, A. Califano, A. Carbone, L. Fantoni, S. Ferrari, A. Gazzola, A. Gloghini, S. Righi, M. Rossi, et al. Gene Expression Analysis of Angioimmunoblastic Lymphoma Indicates Derivation from T Follicular Helper Cells and Vascular Endothelial Growth Factor Deregulation Cancer Res., November 15, 2007; 67(22): 10703 - 10710. [Abstract] [Full Text] [PDF] M. Cuadros, E. Honrado, M. Zajac, J. Benitez, B. Martinez-Delgado, S. S. Dave, L. M. Staudt, E. S. Jaffe, R. Milne, J. 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