In vivo modelling of infection-driven childhood leukemia
Overt B cell precursor acute lymphoblastic leukemia (BCP-ALL) development requires a first genetic insult followed by a second hit likely triggered by immune dysregulation during infection exposure in young children. We aim to understand the mechanisms by which infections trigger leukemia development using murine models genetically pre-disposed to leukemia development and combining them with several chronic and acute infection models including the Lymphocytic choriomeningitis (LCMV) and the Vesicular stomatitis (VSV) viruses. This allows us to investigate the interaction of the pre-leukemic clone with immune subsets in the bone marrow microenvironment and determine their contribution to leukemia development. Using a variety of in vivo and ex vivo models, we also study how trained immunity of innate myeloid cells affects the development and immune responses of the pre-leukemic clone.
Selected Publications:
Liu W, Stachura P, Xu HC, Váraljai R, Shinde P, Umesh Ganesh N, Mack M, Van Lierop A, Huang A, Sundaram B, Lang KS, Picard D, Fischer U, Remke M, Homey B, Roesch A, Haussinger D, Lang PA, Borkhardt A, Pandyra AA.BAFF attenuates immunosuppressive
monocytes in the melanoma tumor microenvironment. Cancer Res, 2021.
Vicente Dueñas C, Janssen S, Oldenburg M, Auer F, González Herrero I, Casado-García A, Isidro-Hernández M, Raboso-Gallego J, Westhoff P, Pandyra AA, Hein D, Gössling KL, Alonso-López D, De Las Rivas J, Bhatia S, Garcia-Criado FJ, García Cenador MB, Weber APM, Köhrer K, Hauer J, Fischer U, Sanchez-Garcia I, Borkhardt A. An intact gut microbiome protects genetically predisposed mice against leukemia. Blood; 2020, 136:2003-2017.
Martín-Lorenzo A, Auer F, Chan LN, García-Ramírez I, González-Herrero I, Rodríguez-Hernández G, Bartenhagen C, Dugas M, Gombert M, Ginzel S, Blanco O, Orfao A, Alonso-López D, Rivas JL, García-Cenador MB, García-Criado FJ, Müschen M, Sánchez-García I, Borkhardt A, Vicente-Dueñas C, Hauer J. Loss of Pax5 Exploits Sca1-BCR-ABLp190 Susceptibility to Confer the Metabolic Shift Essential for pB-ALL. Cancer Res; 2018, 78:2669-2679.
Lang KS*, Lang PA*, Meryk A*, Pandyra AA*, Boucher LM, Pozdeev VI, Tusche MW, Göthert JR, Haight J, Wakeham A, You-Ten AJ, McIlwain DR, Merches K, Khairnar V, Recher M, Nolan GP, Hitoshi Y, Funkner P, Navarini AA, Verschoor A, Shaabani N, Honke N, Penn LZ, Ohashi PS, Häussinger D, Lee KH, Mak TW. Involvement of Toso in activation of monocytes, macrophages, and granulocytes. Proc Natl Acad Sci U S A; 2013, 110:2593-2598.
Xu HC*, Grusdat M*, Pandyra AA, Polz R, Huang J, Sharma P, Deenen R, Köhrer K, Rahbar R, Diefenbach A, Gibbert K, Löhning M, Höcker L, Waibler Z, Häussinger D, Mak TW, Ohashi PS, Lang KS, Lang PA. Type I interferon protects antiviral CD8+ T cells from NK cell cytotoxicity. Immunity; 2014, 40:949-960.
Das Team:
