Project description:Acadesine is a nucleoside analogue with known antileukemic effects in different neoplasms. We investigated the activity of acadesine ne exerts a cytotoxic effect in MCL and synergizes with rituximab supporting clinical examination of this strategy for MCL patients We used microarrays to detail the gene expression changes in acadesine-, rituximab- and combination-treated tumors. Global RNA expression in tumors treated with acadesine, rituximab and the combination in a xenograft model of MCL (Jeko-1). Tumors were collected 18 days after the initiation of the treatments.
Project description:Patients with conventional mantle cell lymphoma (MCL) show an aggressive clinical behavior. However, cases fulfilling the WHO criteria for MCL, but that remain asymptomatic without treatment, have been reported. In an attempt to understand this heterogeneity, we have compared 17 typical cases of MCL with a homogeneous group of 13 asymptomatic individuals with monoclonal expansion of t(11;14)(q13;q32) cyclin D1-positive B-cells in peripheral blood (MALD1). None of these cases have received treatment (minimum follow-up of 26 months; median, 71 months). Gene expression analysis has shown enrichment of signatures associated to neoplastic behavior and cell proliferation in MCL but not in MALD1. In contrast, MALD1 was highly enriched in gene sets related to immune activation and inflammatory responses. CD38 and CD200 genes were differentially expressed between MCL and MALD1. The combined assessment of both proteins by flow cytometry allowed classifying 85% of MALD1 cases. In summary, we have shown for the first time that MALD1, in contrast to MCL, is characterized by immune activation and driven by inflammatory cues. We have also shown that CD38 and CD200 flow cytometry assessment is useful to discern most cases of MALD1 from MCL in the clinical setting. MALD1 should be identified and segregated from the current MCL category to avoid overdiagnosis and unnecessary treatment. 18 samples were analyzed: 5 MALD1, 5 MCL and 8 Healthy Controls
Project description:To analyze the molecular mechanisms by which MCL may induce apoptosis, microarray gene expression profiling of MCL-treated KG1a cells was performed.