Estudio molecular y funcional del linfoma malt

Résumé

The mucosa-associated lymphoid tissue (MALT) lymphoma accounts for 8% of all non-Hodgkin lymphomas. The most characteristic feature of MALT lymphoma is the presence of one of three chromosomal translocations which entail the over expression of either MALT1, BCL10 or the chimeric protein API2-MALT1. In order to evaluate the oncogenic potential of these genomic alterations, both genes and the gene fusion where cloned into the expression vector pcDNA3.1 and subsequently transfected into the BaF3 murine B cell line. All the transgenes activated the NF-kB pathway when over-expressed in these cells. In addition, MALT1 over-expression conferred IL-3 independent growth to BaF3 cells, and caused an aggressive leukemia when injected intravenously in Balb/c Nude mice. In contrast, mice injected with BaF3 cells over-expressing BCL10 or API2-MALT1 did not show survival differences in comparison to controls injected with cells transfected with the empty vector. In addition, we have investigated the molecular pathogenesis of MALT lymphomas by means of gene expression microarray studies. MALT lymphomas share a molecular signature that distinguish them from other B cell malignancies and is composed of genes typically expressed in mucosa-associated lymphoid tissue, epithelial cells and inflammatory cells. The expression of these genes in MALT lymphoma resembles that of marginal B cells, T cells and memory B lymphocytes. Molecular Pathway Analyses of the differentially expressed gene data showed that both MALT lymphoma and Activated large B Cell Lymphomas shared B cell receptor dependent NF-kB activation. Besides, the PI3K-AKT-mTOR and glucocorticoid signaling pathways where deregulated in MALT Lymphoma, underscoring the importance of the deregulation of inflammatory processes in MALT Lymphoma pathogenesis.