| 研究実績の概要 |
UTX, an X-linked histone demethylase, is inactivated/deleted in 1.5-4% of multiple myeloma (MM) patients. Here, we report a novel mouse model in which conditional deletion of Utx in germinal center (GC) derived cells collaborates with the activating Braf V600E mutation to induce GC/post-GC B cell malignancies including MM-like disease. Expansion of clonal plasma cells in the bone marrow, serum M proteins and anemia were observed in MM-like mice. We found that cIDR domain is mostly responsible for the tumor suppressor function of UTX in MM cells. We noted mild induction of MM-like profiles of transcriptome, chromatin accessibility, and H3K27 acetylation in the mice. Plasma cells gradually transformed through induction of Myc. Our study underlies the tumor suppressor function of UTX in MM.
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