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.
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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.