Splenic marginal zone lymphoma (SMZL)is a newly recognized lymphoma type whose precise molecular pathogenesis is still essentially unknown. This hampers differential diagnosis with other small Bcell malignancies. With the aim of characterizing this tumor more comprehensively, and of identifying new diagnostic and prognostic markers, we performed cDNA microarray expression profiling and tissue microarray (TMA) immunohistochemical studies in a relatively large series of 44 SMZLs. The results were related to immunoglobulin heavy chain variable region (IgV H ) mutational status and clinical outcome. SMZLs display a largely homogenous signature, implying the existence of a single molecular entity. Of the genes deregulated in SMZLs, special mention may be made of the genes involved in B-cell receptor (BCR) signaling, tumor necrosis factor (TNF) signaling and nuclear factor-B (NF-B) activation, such as SYK, BTK, BIRC3, TRAF3, and LTB. Other genes observed were SELL and LPXN, which were highly expressed in spleen, and lymphoma oncogenes, such as ARHH and TCL1. In contrast, the genes CAV1, CAV2, and GNG11 located in 7q31, a commonly deleted area, were downregulated in the entire series. A comparison with the genes comprising the signature of other small B-cell lymphomas identified 3 genes whose expression distinguishes SMZL, namely ILF1, SENATAXIN, and CD40.
IntroductionSplenic marginal zone lymphoma (SMZL) is a newly described lymphoma type, whose precise diagnosis, patient stratification into risk groups, and appropriate treatment is still in need of further investigation. [1][2][3] The diagnosis of SMZL is often hindered by the lack of conclusive immunophenotypical or molecular data concerning differences from chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). The expression of CyclinD1 and B-cell lymphoma 6 (Bcl6) can contribute to the diagnosis of MCL or FL, but this is occasionally difficult to measure in samples of peripheral blood or bone marrow from CLL and MCL cases. Consequently, the diagnosis of SMZL is still characterized by strikingly low reproducibility. Even when a correct diagnosis has been established, the clinical course is appreciably variable, with a subset of cases showing frequent and early relapses, and shorter survival. Although patients with this aggressive SMZL form can be recognized by the absence of immunoglobulin heavy chain variable region (IgV H ) somatic mutation or the 7q31 deletion, 4 this is not accurate enough to allow stratification of patients into different risk groups receiving risk-adjusted specific treatments. Finally, the available treatments for SMZL essentially overlap those of other small B-cell non-Hodgkin lymphomas (NHLs), and the molecular data obtained so far for SMZL are insufficient to form the basis for the proposal of new therapeutic targets.Lymphoma diagnosis and knowledge has been facilitated in recent years by the development of high-throughput molecular tools, such as expression microarrays aimed at quantifying the expr...
