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Title: | Mouse models of human multiple myeloma subgroups |
Author: | 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 |
Keywords: | Mieloma múltiple Ratolins (Animals de laboratori) Multiple Myeloma Mice |
Issue Date: | 28-Feb-2023 |
Publisher: | Proceedings of the National Academy of Sciences |
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. |
Note: | Reproducció del document publicat a: https://doi.org/10.1073/pnas.2219439120 |
It is part of: | Proceedings of the National Academy of Sciences, 2023, vol. 120, num. 10 |
URI: | http://hdl.handle.net/2445/208404 |
Related resource: | https://doi.org/10.1073/pnas.2219439120 |
ISSN: | 1091-6490 |
Appears in Collections: | Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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