The role of EZH2, a histone methyltransferase, recently implicated in human myeloid and lymphoid malignancies, will be studied in models of B-lymphoid tumorigenesis and myeloid leukemogenesis. Tumors are established in mice bearing a floxed copy of the endogenous Ezh2 gene (floxed evolutionary conserved SET domain). Ezh2 will then be deleted in established tumor cell lines by infection with Cre-expressing viruses and in vitro as well as in vivo effects will be analyzed. In addition, tumor development in mice with B-cell-specific and myeloid-specific deletion of Ezh2 will be investigated. Consequences for epigenetic modifications and gene expression will be determined.
Marinkovic D, Marinkovic T, Schreiner B, Hess J, Wirth T. Reversible lymphomagenesis in conditionally c-MYC expressing mice. Int J Cancer. 2004;110:336-342.
Marinkovic D, Marinkovic T, Kokai E, Wirth T. Identification of novel c-Myc target genes with a potential role in lymphomagenesis. Nucl Acids Res. 2004;32:5368-5378.
Ushmorov A, Ritz O, Hummel M, Leithäuser F, Möller P, Stein H, Wirth T. Epigenetic silencing of the immunoglobulin heavy chain gene in classical Hodgkin lymphoma-derived cell lines contributes to the loss of immunoglobulin expression. Blood. 2004;104:3326-3334.
Ushmorov A, Leithauser F, Sakk O, Weinhausel A, Popov SW, Moller P, Wirth T. Epigenetic processes play a major role in B-cell-specific gene silencing in classical Hodgkin lymphoma. Blood. 2006;107:2493-2500.
Ushmorov A, Leithäuser F, Ritz O, Barth TF, Möller P, Wirth T. ABF-1 is frequently silenced by promoter methylation in follicular lymphoma, diffuse large B-cell lymphoma and Burkitt's lymphoma. Leukemia. 2008;22:1942-1944.
Sander S, Bullinger L, Klapproth K, Fiedler K, Kestler HA, Barth TFE, Möller P, Stilgenbauer S, Pollack JR, Wirth T. MYC stimulates EZH2 expression by repression of its negative regulator miR-26a. Blood. 2008;112:4202-4212.
Sander S, Bullinger L, Wirth T. Repressing the repressor - a new mode of MYC action in lymphomagenesis. Cell Cyle. 2009;8:556-559.