Preclinical models of human multiple myeloma subgroups
Preclinical models of human multiple myeloma subgroups
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 subgroup-specific MM models by the GC B cell-specific co-activation of Ccnd1 or MMSET with a constitutively active Ikk2 mutant, mimicking the secondary NFκB 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 transcriptional profiles resembling their human counterparts. Thus, we show that Ccnd1 and MMSET cooperate with NFκB in MM pathogenesis, considering for the first time the genetic heterogeneity of MM for the generation of preclinical models.
Blanc Eric、Napieczynska Hanna、Walter Barbara、Wollert-Wulf Brigitte、Rajewsky Klaus、Beule Dieter、Anagnostopoulos Ioannis、Janz Martin、Winkler Wiebke、D¨aaz Carlota Farr¨|、Werner Marvin、Heuser Arnd、Yasuda Tomoharu、Mathas Stephan、Rosenwald Andreas、Langner Patrick
Charit¨| Universit?tsmedizin Berlin, Corporate Member of Freie Universit?t Berlin, Humboldt-Universit?t zu Berlin, and Berlin Institute of Health, Core Unit Bioinformatics (CUBI)Animal Phenotyping, Max Delbr¨1ck Center for Molecular Medicine in the Helmholtz AssociationBiology of Malignant Lymphomas, Experimental and Clinical Research Center, Max Delbr¨1ck Center for Molecular Medicine in the Helmholtz Association and Charit¨| Universit?tsmedizinBiology of Malignant Lymphomas, Experimental and Clinical Research Center, Max Delbr¨1ck Center for Molecular Medicine in the Helmholtz Association and Charit¨| Universit?tsmedizinImmune Regulation and Cancer, Max Delbr¨1ck Center for Molecular Medicine in the Helmholtz AssociationCharit¨| Universit?tsmedizin Berlin, Corporate Member of Freie Universit?t Berlin, Humboldt-Universit?t zu Berlin, and Berlin Institute of Health, Core Unit Bioinformatics (CUBI)Institute of Pathology, Universit?t W¨1rzburg and Comprehensive Cancer Centre Mainfranken (CCCMF)Biology of Malignant Lymphomas, Experimental and Clinical Research Center, Max Delbr¨1ck Center for Molecular Medicine in the Helmholtz Association and Charit¨| Universit?tsmedizinImmune Regulation and Cancer, Max Delbr¨1ck Center for Molecular Medicine in the Helmholtz Association||Biology of Malignant Lymphomas, Experimental and Clinical Research Center, Max Delbr¨1ck Center for Molecular Medicine in the Helmholtz Association and Charit¨| Universit?tsmedizinImmune Regulation and Cancer, Max Delbr¨1ck Center for Molecular Medicine in the Helmholtz Association||Biology of Malignant Lymphomas, Experimental and Clinical Research Center, Max Delbr¨1ck Center for Molecular Medicine in the Helmholtz Association and Charit¨| Universit?tsmedizinBiology of Malignant Lymphomas, Experimental and Clinical Research Center, Max Delbr¨1ck Center for Molecular Medicine in the Helmholtz Association and Charit¨| Universit?tsmedizinAnimal Phenotyping, Max Delbr¨1ck Center for Molecular Medicine in the Helmholtz AssociationImmune Regulation and Cancer, Max Delbr¨1ck Center for Molecular Medicine in the Helmholtz AssociationBiology of Malignant Lymphomas, Experimental and Clinical Research Center, Max Delbr¨1ck Center for Molecular Medicine in the Helmholtz Association and Charit¨| Universit?tsmedizinInstitute of Pathology, Universit?t W¨1rzburg and Comprehensive Cancer Centre Mainfranken (CCCMF)Animal Phenotyping, Max Delbr¨1ck Center for Molecular Medicine in the Helmholtz Association
肿瘤学基础医学医学研究方法
Blanc Eric,Napieczynska Hanna,Walter Barbara,Wollert-Wulf Brigitte,Rajewsky Klaus,Beule Dieter,Anagnostopoulos Ioannis,Janz Martin,Winkler Wiebke,D¨aaz Carlota Farr¨|,Werner Marvin,Heuser Arnd,Yasuda Tomoharu,Mathas Stephan,Rosenwald Andreas,Langner Patrick.Preclinical models of human multiple myeloma subgroups[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2021.08.28.458010.点此复制
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