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Blood, 1 April 2004, Vol. 103, No. 7, pp. 2727-2737.
Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-06-2160.
Submitted June 30, 2003
Accepted September 29, 2003
Small lymphocytic lymphoma (SLL), marginal zone B-cell lymphoma (MZL), mantle cell lymphoma (MCL) exhibit distinct gene-expression profiles allowing molecular diagnosis
Catherine Thieblemont*, Valery Nasser, Pascale Felman, Karen Leroy, Sophie Gazzo, Evelyne Callet-Bauchu, Beatrice Loriod, Samuel Granjeaud, Philippe Gaulard, Corinne Haioun, Alexandra Traverse-Glehen, Lucile Baseggio, Francois Bertucci, Daniel Birnbaum, Florence Magrangeas, Stephane Minvielle, Herve Avet-Loiseau, Gilles Salles, Bertrand Coiffier, Francoise Berger, and Remi Houlgatte
Centre Hospitalier Lyon-sud - Hospices civils de Lyon, Service d'Hematologie, Pierre-Benite, France; Universite Claude Bernard-Lyon 1, Equipe d'Accueil, Lyon, France
INSERM ERM206, TAGC, Marseille, France
Institut Paoli-Calmettes, Departement d'Oncologie moleculaire Institut Paoli-Calmettes, Marseille, France
Centre Hospitalier Lyon-sud, Service d'Hematologie cellulaire Centre Hospitalier Lyon-sud, Pierre-Benite, France
Hopital Henri Mondor, Departement de Pathologie, EA2348 Hopital Henri Mondor, Creteil, France
Hopital Henri Mondor, Service d'Hematologie, Creteil, France
Centre Hospitalier Lyon-Sud, Service d'Anatomie Pathologique, Pierre-Benite, France
INSERM, Unite 463, Nantes, France
Universite Claude Bernard-Lyon 1, Equipe d'Accueil, Lyon, France; Centre Hospitalier Lyon-Sud, Service d'Anatomie Pathologique, Pierre-Benite, France
* Corresponding author; email: catherine.thieblemont{at}chu-lyon.fr.
Non-germinal center small B-cell lymphomas represent a heterogeneous group of non-Hodgkin's lymphomas, the most frequent histological subtypes being small lymphocytic lymphoma (SLL), splenic marginal zone B-cell lymphoma (MZL), and mantle cell lymphoma (MCL). In order to identify genomic signatures specific for each disease, we analyzed 128 primary tumors using high density microarrays. Several clusters of genes significantly discriminated the three histological subtypes. Genes associated with cell-adhesion, angiogenesis and inhibition of apoptosis were up-regulated in SLL. Genes associated with intracellular signalling via the AKT1 pathway were up-regulated in splenic MZL. Genes associated with cell cycle control and multidrug resistance were upregulated in MCL. Using 44 genes selected within the gene clusters discriminant for the three lymphoma subtypes, we generated a class prediction score that allowed to classify the three entities in 96% of the cases, including borderline cases. Whereas specific transcriptional profiles easily distinguished all MZL samples, SLL samples and most of the MCL samples, into separate groups, few MCL cases exhibited MZL-type transcriptional profiles. This study demonstrates that SLL, splenic MZL and MCL possess specific transcriptional profiles that may be relevant to the pathogenesis and the diagnosis of these histological subtypes.
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