|
Our research group was one of the first that showed an association of Helicobacter pylori (H.p.) infection with the development of gastric MALT lymphoma (Bayerdorffer et al., Lancet 1995; Neubauer et al., J Natl Cancer Inst 1997; Wündisch et al., JCO 2005). We have shown that the genetic profile of H.p.-induced early gastric MALT lymphoma distinctly differed from tissue of chronic gastritis. Up-regulation of Phospholipase C γ2 (PLCγ2) in gastric MALT lymphoma, which leads to activation of NF-kB, was one of the most interesting finding (Huynh et al. Leukemia Lymphoma 2008).
Different genetic host factors are associated with increased risk of developing gastric MALT lymphomas. These are e.g. polymorphism in IL-1, CTLA4, GST-T1 and TNF-alpha (Rollinson et al., Blood 2003; Wu et al., Haematologica 2005; Wu et al., Int J Cancer 2004). All of these host factors result in deregulated inflammation after H.p. infection.
Mice with gain-of-function mutation in PLC γ2 show autoimmunity and inflammatory disease (Yu et al., Immunity 2005). In this project we want to infect these mice with Helicobacter felis. As control groups serve wt mice and in further studies PLCγ2-knockout mice. Our hypothesis is that Balb/c mice with gain-of-function in PLCγ2 develop earlier and in a higher frequency MALT lymphomas compared to control groups.
References:
Bayerdörffer E, Neubauer A, Rudolph B, Thiede C, Lehn N, Eidt S, Stolte M. (1995).
Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. MALT Lymphoma Study Group. Lancet 345(8965):1591-4.
Neubauer A, Thiede C, Morgner A, Alpen B, Ritter M, Neubauer B, Wündisch T, Ehninger G, Stolte M, Bayerdörffer E. (1997). Cure of Helicobacter pylori infection and duration of remission of low-grade gastric mucosa-associated lymphoid tissue lymphoma. J Natl Cancer Inst 17;89(18):1350-5.
Wündisch T, Thiede C, Morgner A, Dempfle A, Günther A, Liu H, Ye H, Du MQ, Kim TD, Bayerdörffer E, Stolte M, Neubauer A. (2005). Long-term follow-up of gastric MALT lymphoma after Helicobacter pylori eradication. J Clin Oncol. 23(31):8018-24.
Huynh MQ, Wacker HH, Wündisch T, Sohlbach K, Daniel Kim T, Krause M, Stabla K, Roth P, Fischbach W, Stolte M, Neubauer A. (2008). Expression profiling reveals specific gene expression signatures in gastric MALT lymphomas. Leuk Lymphoma. 49(5):974-83.
Rollinson S, Levene AP, Mensah FK, Roddam PL, Allan JM, Diss TC, Roman E, Jack A, MacLennan K, Dixon MF, Morgan GJ. (2003). Gastric marginal zone lymphoma is associated with polymorphisms in genes involved in inflammatory response and antioxidative capacity. Blood. 102(3):1007-11.
Wu KL, van Wieringen W, Vellenga E, Zweegman S, Lokhorst HM, Sonneveld P. (2005).
Analysis of the efficacy and toxicity of bortezomib for treatment of relapsed or refractory multiple myeloma in community practice. Haematologica 90(7):996-7.
Wu MS, Chen LT, Shun CT, Huang SP, Chiu HM, Wang HP, Lin MT, Cheng AL, Lin JT. (2004). Promoter polymorphisms of tumor necrosis factor-alpha are associated with risk of gastric mucosa-associated lymphoid tissue lymphoma. Int J Cancer 110(5):695-700.
Yu P, Constien R, Dear N, Katan M, Hanke P, Bunney TD, Kunder S, Quintanilla-Martinez L, Huffstadt U, Schröder A, Jones NP, Peters T, Fuchs H, de Angelis MH, Nehls M, Grosse J, Wabnitz P, Meyer TP, Yasuda K, Schiemann M, Schneider-Fresenius C, Jagla W, Russ A, Popp A, Josephs M, Marquardt A, Laufs J, Schmittwolf C, Wagner H, Pfeffer K, Mudde GC. (2005). Autoimmunity and inflammation due to a gain-of-function mutation in phospholipase C gamma 2 that specifically increases external Ca2+ entry. Immunity 22(4):451-65.
|
