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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/208404
Mouse models of human multiple myeloma subgroups
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Multiple myeloma (MM), a tumor of germinal center (GC)-experienced plasma cells, comprises distinct genetic subgroups, such as the t(11;14)/CCND1 and the t(4;14)/MMSET subtype. We have generated genetically defined, subgroup-specific MM models by the GC B cell-specific coactivation of mouse Ccnd1 or MMSET with a constitutively active Ikk2 mutant, mimicking the secondary NF-kappa B activation frequently seen in human MM. Ccnd1/Ikk2ca and MMSET/Ikk2ca mice developed a pronounced, clonally restricted plasma cell outgrowth with age, accompanied by serum M spikes, bone marrow insufficiency, and bone lesions. The transgenic plasma cells could be propagated in vivo and showed distinct transcriptional profiles, resembling their human MM counterparts. Thus, we show that targeting the expression of genes involved in MM subgroup-specific chromosomal translocations into mouse GC B cells translates into distinct MM-like diseases that recapitulate key features of the human tumors, opening the way to a better understanding of the pathogenesis and therapeutic vulnerabilities of different MM subgroups.
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WINKLER, Wiebke, FARRÉ DÍAZ, Carlota, BLANC, Eric, NAPIECZYNSKA, Hanna, LANGNER, Patrick, WERNER, Marvin, WALTER, Barbara, WOLLERT WULF, Brigitte, YASUDA, Tomoharu, HEUSER, Arnd, BEULE, Dieter, MATHAS, Stephan, ANAGNOSTOPOULOS, Ioannis, ROSENWALD, Andreas, RAJEWSKY, Klaus, JANZ, Martin. Mouse models of human multiple myeloma subgroups. _Proceedings of the National Academy of Sciences_. 2023. Vol. 120, núm. 10. [consulta: 25 de febrer de 2026]. ISSN: 1091-6490. [Disponible a: https://hdl.handle.net/2445/208404]