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2 results on '"Yumiko Tomoe"'

1. A novel Menin-MLL1 inhibitor, DS-1594a, prevents the progression of acute leukemia with rearranged MLL1 or mutated NPM1

Author

Masashi Numata, Noriyasu Haginoya, Machiko Shiroishi, Tsuyoshi Hirata, Aiko Sato-Otsubo, Kenji Yoshikawa, Yoshimi Takata, Reina Nagase, Yoshinori Kashimoto, Makoto Suzuki, Nina Schulte, Gernot Polier, Akiko Kurimoto, Yumiko Tomoe, Akiko Toyota, Tomoko Yoneyama, Emi Imai, Kenji Watanabe, Tomoaki Hamada, Ryutaro Kanada, Jun Watanabe, Yoshiko Kagoshima, Eri Tokumaru, Kenji Murata, Takayuki Baba, Taeko Shinozaki, Masami Ohtsuka, Koichi Goto, Tsuyoshi Karibe, Takao Deguchi, Yoshihiro Gocho, Masanori Yoshida, Daisuke Tomizawa, Motohiro Kato, Shinji Tsutsumi, Mayumi Kitagawa, and Yuki Abe

Subjects
Menin-MLL1 inhibitor, MLL1-r or NPM1c acute leukemia, Leukemia-initiating cells, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282, Cytology, QH573-671
Abstract

Abstract Background Mixed lineage leukemia 1-rearranged (MLL1-r) acute leukemia patients respond poorly to currently available treatments and there is a need to develop more effective therapies directly disrupting the Menin‒MLL1 complex. Small-molecule–mediated inhibition of the protein‒protein interaction between Menin and MLL1 fusion proteins is a potential therapeutic strategy for patients with MLL1-r or mutated-nucleophosmin 1 (NPM1c) acute leukemia. In this study, we preclinically evaluated the new compound DS-1594a and its salts. Methods We evaluated the preclinical efficacy of DS-1594a as well as DS-1594a·HCl (the HCl salt of DS-1594a) and DS-1594a·succinate (the succinic acid salt of DS-1594a, DS-1594b) in vitro and in vivo using acute myeloid leukemia (AML)/acute lymphoblastic leukemia (ALL) models. Results Our results showed that MLL1-r or NPM1c human leukemic cell lines were selectively and highly sensitive to DS-1594a·HCl, with 50% growth inhibition values

Published
2023
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2. Requirements for multivalent Yb body assembly in transposon silencing in Drosophila

Author

Shigeki Hirakata, Yumiko Tomoe, Hirotsugu Ishizu, Aoi Fujita, and Mikiko C. Siomi

Subjects
Transposable element, endocrine system, Somatic cell, Piwi-interacting RNA, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, Protein Domains, Genetics, Gene silencing, Animals, Drosophila Proteins, Gene Silencing, RNA, Small Interfering, Molecular Biology, 030304 developmental biology, 0303 health sciences, biology, Chemistry, Ovary, Helicase, RNA, RNA Helicase A, Cell biology, Drosophila melanogaster, biology.protein, DNA Transposable Elements, Female, Protein Multimerization, 030217 neurology & neurosurgery, Biogenesis, Protein Binding, Reports
Abstract

Female sterile (1) Yb (Yb) is a primary component of Yb bodies, perinuclear foci considered to be the site of PIWI-interacting RNA (piRNA) biogenesis in Drosophila ovarian somatic cells (OSCs). Yb consists of three domains: Helicase C-terminal (Hel-C), RNA helicase, and extended Tudor (eTud) domains. We previously showed that the RNA helicase domain is necessary for Yb-RNA interaction, Yb body formation, and piRNA biogenesis. Here, we investigate the functions of Hel-C and eTud and reveal that Hel-C is dedicated to Yb-Yb homotypic interaction, while eTud is necessary for Yb-RNA association, as is the RNA helicase domain. All of these domains are indispensable for Yb body formation and transposon-repressing piRNA production. Strikingly, however, genic piRNAs unrelated to transposon silencing are produced in OSCs where Yb bodies are disassembled. We also reveal that Yb bodies are liquid-like multivalent condensates whose assembly depends on Yb-Yb homotypic interaction and Yb binding particularly with flamenco RNA transcripts, the source of transposon-repressing piRNAs. New insights into Yb body assembly and biological relevance of Yb bodies in transposon silencing have emerged.

Published
2019

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