Protein kinases and phosphatases in B-cell lymphoma

University dissertation from Inst för Laboratoriemedicin, Avd för tumörbiologi, Malmö Universitetssjukhus, Lunds Universitet

Abstract: Around 2000 persons are diagnosed with lymphoma in Sweden each year. There are many subgroups described for this form of cancer and the great majority is derived from B-cells. The most common subgroup is Diffuse large B-cell lymphoma (DLBCL), a highly aggressive disease where only half of the patients are cured. The lymphoma types seen in adults and children vary and the dominant form in children is the B-cell derived Burkitt lymphoma (BL). In contrast to DLBCL, high survival rates in BL are obtained but more research on normal- and tumor B-cells is needed for a better understanding of the cellular mechanisms underlying lymphoma pathogenesis. Phosphorylation and dephosphorylation of enzymes are key events in signal transduction in cells. Protein kinases phosphorylate enzymes while protein phosphatases dephosphorylate them, and these opposite actions must be carefully balanced for normal cell division to occur. The aim of this study was to characterize B-cell lymphomas with emphasis on a panel of kinases and phosphatases previously described as oncogenes (kinases) and tumorsuppressors (phosphatases) in human cancers. We analyzed DLBCL tissue and found the kinases PKC-? II and ZAP70 to be stronger expressed at protein level in a subgroup of the disease associated with poor survival. We further report enhanced activation of DLBCL cells through the B-cell receptor when ZAP70 is introduced. Also, the protein expression of the phosphatases HePTP and PTEN are weaker in BL tissue from children compared to in non-malignant pediatric controls. Our results indicate important roles for the described kinases and phosphatases in B-cell lymphomas.

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