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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.
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NEOPLASIA
Small lymphocytic lymphoma, marginal zone B-cell lymphoma, and mantle cell lymphoma exhibit distinct gene-expression profiles allowing molecular diagnosis
Catherine Thieblemont,
Valéry Nasser,
Pascale Felman,
Karen Leroy,
Sophie Gazzo,
Evelyne Callet-Bauchu,
Béatrice Loriod,
Samuel Granjeaud,
Philippe Gaulard,
Corinne Haioun,
Alexandra Traverse-Glehen,
Lucile Baseggio,
François Bertucci,
Daniel Birnbaum,
Florence Magrangeas,
Stéphane Minvielle,
Hervé Avet-Loiseau,
Gilles Salles,
Bertrand Coiffier,
Françoise Berger, and
Rémi Houlgatte
From the Service d'Hématologie, the Service d'Hématologie cellulaire, and the Service d'anatomie pathologique, Centre Hospitalier Lyon-Sud, Hospices civils de Lyon, Pierre-Bénite; Equipe d'Accueil "Pathologie des cellules lymphoides," Université Claude Bernard-Lyon 1, Lyon; TAGC, INSERM ERM206, and the Département d'oncologie moléculaire, Institut Paoli-Calmettes, Marseille; Département de Pathologie, EA2348, Hôpital Henri Mondor, AP-HP, and the Service d'Hématologie, Hôpital Henri Mondor, Créteil; and INSERM U463, Nantes, France.
Non-germinal center small B-cell lymphomas represent a heterogeneous group of non-Hodgkin lymphomas, the most frequent histologic 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 3 histologic subtypes. Genes associated with cell adhesion, angiogenesis, and inhibition of apoptosis were up-regulated in SLL. Genes associated with intracellular signaling via the AKT1 pathway were up-regulated in splenic MZL. Genes associated with cell cycle control and multidrug resistance were up-regulated in MCL. Using 44 genes selected within the gene clusters discriminant for the 3 lymphoma subtypes, we generated a class prediction score that allowed us to classify the 3 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 histologic subtypes. (Blood. 2004;103:2727-2737)
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