Page 124 - Haematologica - Vol. 105 n. 6 - June 2020

Non-Hodgkin Lymphoma
Ferrata Storti Foundation
Haematologica 2020 Volume 105(6):1582-1592
Defining signatures of peripheral T-cell lymphoma with a targeted 20-marker gene expression profiling assay
Fanny Drieux,1,2,3* Philippe Ruminy,1* Ahmad Abdel-Sater,1 François Lemonnier,3,4 Pierre-Julien Viailly,1 Virginie Fataccioli,3 Vinciane Marchand,1 Bettina Bisig,5 Audrey Letourneau,5 Marie Parrens,6 Céline Bossard,7 Julie Bruneau,8 Pamela Dobay,5 Liana Veresezan,1,2 Aurélie Dupuy,3 Anaïs Pujals,3,9 Cyrielle Robe,3 Nouhoum Sako,3 Christiane Copie-Bergman,3,9 Marie-Hélène Delfau-Larue,3,10 Jean-Michel Picquenot,1,2 Hervé Tilly,1 Richard Delarue,11
Fabrice Jardin,
1#
Laurence de Leval
5# 3,9# and Philippe Gaulard
1INSERM U1245, Centre Henri Becquerel, Rouen, France; 2Service d’Anatomie et Cytologie Pathologiques, Centre Henri Becquerel, Rouen, France; 3INSERM U955 and Université Paris-Est, Créteil, France; 4Unité Hémopathies Lymphoïdes, Groupe Hospitalier Henri Mondor, AP-HP, Créteil, France; 5Institut de Pathologie, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland; 6Service d’Anatomie et Cytologie Pathologiques, Hôpital Haut-Lévêque, CHU de Bordeaux, France; 7Service d’Anatomie et Cytologie Pathologiques, CHU de Nantes, France; 8Service d’Anatomie et Cytologie Pathologiques, Hôpital Universitaire Necker - Enfants Malades, Assistance Publique - Hôpitaux de Paris (APHP), Paris, France; 9Département de Pathologie, Groupe Hospitalier Henri Mondor, AP-HP, Créteil, France; 10Département d’Hématologie et Immunologie Biologique, Groupe Hospitalier Henri Mondor, AP-HP, Créteil, France and 11Service Hématologie Adultes, Hôpital Universitaire Necker - Enfants Malades, Assistance Publique - Hôpitaux de Paris (APHP), Paris, France
*FD and PR contributed equally as co-first authors.
#FJ, LdL and PG contributed equally as co-senior authors.
ABSTRACT
Peripheral T-cell lymphoma comprises a heterogeneous group of mature non-Hodgkin lymphomas. Their diagnosis is challenging, with up to 30% of cases remaining unclassifiable and referred to as “not otherwise specified”. We developed a reverse transcriptase-multi- plex ligation-dependent probe amplification gene expression profiling assay to differentiate the main T-cell lymphoma entities and to study the heterogeneity of the “not specified” category. The test evaluates the expression of 20 genes, including 17 markers relevant to T-cell immunol- ogy and lymphoma biopathology, one Epstein-Barr virus-related tran- script, and variants of RHOA (G17V) and IDH2 (R172K/T). By unsuper- vised hierarchical clustering, our assay accurately identified 21 of 21 ALK-positive anaplastic large cell lymphomas, 16 of 16 extranodal natu- ral killer (NK)/T-cell lymphomas, 6 of 6 hepatosplenic T-cell lymphomas, and 13 of 13 adult T-cell leukemia/lymphomas. ALK-negative anaplastic lymphomas (n=34) segregated into one cytotoxic cluster (n=10) and one non-cytotoxic cluster expressing Th2 markers (n=24) and enriched in DUSP22-rearranged cases. The 63 TFH-derived lymphomas divided into two subgroups according to a predominant TFH (n=50) or an enrichment in Th2 (n=13) signatures. We next developed a support vector machine predictor which attributed a molecular class to 27 of 77 not specified T- cell lymphomas: 17 TFH, five cytotoxic ALK-negative anaplastic and five NK/T-cell lymphomas. Among the remaining cases, we identified two cell-of-origin subgroups corresponding to cytotoxic/Th1 (n=19) and Th2 (n=24) signatures. A reproducibility test on 40 cases yielded a 90% con- cordance between three independent laboratories. This study demon- strates the applicability of a simple gene expression assay for the classi- fication of peripheral T-cell lymphomas. Its applicability to routinely- fixed samples makes it an attractive adjunct in diagnostic practice.
Correspondence:
PHILIPPE GAULARD
philippe.gaulard@aphp.fr
PHILIPPE RUMINY
philippe.ruminy@chb.unicancer.fr
Received: May 9, 2019.
Accepted: September 2, 2019. Pre-published: September 5, 2019.
doi:10.3324/haematol.2019.226647
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/105/6/1582
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