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winkler-et-al-2023-mouse-models-of-human-multiple-myeloma-subgroups.pdf (5.51 MB)

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2023-02-28

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cc by-nc-nd (c) Winkler, Wiebke et al., 2023
Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/208404

Mouse models of human multiple myeloma subgroups

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https://doi.org/10.1073/pnas.2219439120

Abstract

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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Mieloma múltiple, Ratolins (Animals de laboratori)

Subject (English)

Multiple Myeloma, Mice

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Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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WINKLER, Wiebke, et al. Mouse models of human multiple myeloma subgroups. Proceedings of the National Academy of Sciences. 2023. Vol. 120, num. 10. ISSN 1091-6490. [consulted: 15 of August of 2026]. Available at: https://hdl.handle.net/2445/208404

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