Abnormal endosomal traffic induced by Samd9/9L causing myelodysplastic syndromes and inherited bone marrow failure
Project/Area Number |
18H02838
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Single-year Grants |
Section | 一般 |
Review Section |
Basic Section 54010:Hematology and medical oncology-related
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Research Institution | Hiroshima University |
Principal Investigator |
Inaba Toshiya 広島大学, 原爆放射線医科学研究所, 教授 (60281292)
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Co-Investigator(Kenkyū-buntansha) |
長町 安希子 広島大学, 原爆放射線医科学研究所, 助教 (20585153)
松井 啓隆 熊本大学, 大学院生命科学研究部(医), 教授 (60379849)
金井 昭教 広島大学, 原爆放射線医科学研究所, 助教 (60549567)
|
Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2018: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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Keywords | 骨髄異形成症候群 / 造血不全 / モノソミー7 / サイトカイン / Samd9/9L / エンドソーム / 受容体代謝 / MDS / Samd9/9L / サイトカイン受容体 / トランスフェリン / Samd9/L / 表面受容体代謝 / 造血障害 / エンドソーム交通 |
Outline of Final Research Achievements |
Samd9 and Samd9L (hereafter Samd9/9L) are leukemia- and MDS- suppressor genes on 7q. Recent studies have indicated that gain-of-function mutations cause multiple organ failure including inherited bone marrow failure syndromes that are now designated as "Samd9/9L syndrome". Using Crispr/Cas9 technology, we established and analyzed a mice model carrying one of the causing mutations. The endocytosis of ligand-bound growth factors, as well as transferrin receptors was perturbed in the bone marrow, testis and kidney. In addition, enhanced lysosome function promoted cytokine receptor metabolism.
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Academic Significance and Societal Importance of the Research Achievements |
骨髄異形成症候群(MDS)は、白血病と同程度の頻度であり、血液疾患として稀なものではないが、かつて「不応性貧血」とか「くすぶり型白血病」とか呼ばれていたことが端的に示すように、造血不全と腫瘍の両方の性格を持つ難治性疾患である。Samd9/9L遺伝子は、その欠損がMDSを発症することが知られていたが、今回その機能亢進が造血不全を引き起こすことがヒトとマウスで確認された。MDSという難解な疾患の本質に迫る手がかりを与える研究成果であり、海外の研究者からも大きな反響があった。
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Report
(4 results)
Research Products
(23 results)
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[Journal Article] HHEX promotes myeloid transformation in cooperation with mutant ASXL1.2020
Author(s)
Takeda R, Asada S, Park SJ, Yokoyama A, Becker H, Kanai A, Visconte V, Hershberger C, Hayashi Y, Yonezawa T, Tamura M, Fukushima T, Tanaka Y, Fukuyama T, Matsumoto A, Yamasaki S, Nakai K, Yamazaki S, Inaba T, Shibata T, Inoue D, Honda H, Goyama S, Maciejewski J, Kitamura T.
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Journal Title
Blood
Volume: 136
Pages: 1670-1684
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] High prevalence of MEF2D fusion in human B-cell precursor acute lymphoblastic leukemia cell lines.2020
Author(s)
Akahane K, Yasuda T, Tsuzuki S, Hayakawa F, Kiyokawa N, Somazu S, Watanabe A, Kagami K, Abe M, Harama D, Goi K, Kawazu M, Kojima S, Imamura T, Goto H, Iwamoto S, Minegishi M, Abe M, Hojo H, Inaba T, Mano H, Sugita K, Inukai T.
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Journal Title
Hematol Oncol.
Volume: 38
Issue: 4
Pages: 614-617
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Association of aberrant ASNS imprinting with asparaginase sensitivity and chromosomal abnormality in childhood BCP-ALL2020
Author(s)
Atsushi Watanabe, Kunio Miyake, Jessica Nordlund, Ann-Christine Syvanen, Louise van der Weyden, Hiroaki Honda, Norimasa Yamasaki, Akiko Nagamachi, Toshiya Inaba, Tomokatsu Ikawa, Kevin Y Urayama, Nobutaka Kiyokawa, Akira Ohara, Shunsuke Kimura, Yasuo Kubota, Junko Takita, Hiroaki Goto, Kimiyoshi Sakaguchi, et al.
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Journal Title
Blood
Volume: 136
Issue: 20
Pages: 2319-2333
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Molecular pathogenesis of progression to myeloid leukemia from TET-insufficient status.2020
Author(s)
Shrestha R, Sakata-Yanagimoto M, Maie K, Oshima M, Ishihara M, Suehara Y, Fukumoto K,1 Nakajima-Takagi Y, Matsui H, Kato T, Muto H, Sakamoto T, Kusakabe M, Nannya Y, Makishima H, Ueno H, Saiki R, Ogawa S, Chiba K, Shiraishi Y, Miyano S, Mouly E, Bernard OA, Inaba T, Koseki H, Iwama A, Chiba S
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Journal Title
Blood Adv.
Volume: 4(5)
Issue: 5
Pages: 845-854
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Resistance of t(17;19)-acute lymphoblastic leukemia cell lines to multiagents in induction therapy.2019
Author(s)
Watanabe A, Inukai T, Kagami K, Abe M, Takagi M, Fukushima T, Fukushima H, Nanmoku T, Terui K, Ito T, Toki T, Ito E, Fujimura J, Goto H, Endo M, Look T, Kamps M, Minegishi M, Takita J, Inaba T, Takahashi H, Ohara A, Harama D, Shinohara T, Somazu S, Oshiro H, Akahane K, Goi K, Sugita K.
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Journal Title
Cancer Med.
Volume: 7
Issue: 11
Pages: 5274-5288
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Dose-response curves for analyzing of dicentric chromosomes and chromosome translocation following doses of 1,000 mGy or less based on irradiated peripheral blood samples from 5 healthy individuals.2018
Author(s)
Abe Y, Yoshida MA, Fujioka K, Kurosu Y, Ujiie R, Yanagi A, Tsuyama N, Miura T, Inaba T, Kamiya K, Sakai A
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Journal Title
Journal of Radiation Research
Volume: 59
Issue: 1
Pages: 35-42
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A novel ASXL1?OGT axis plays roles in H3K4 methylation and tumor suppression in myeloid malignancies2018
Author(s)
Inoue D, Fujino T, Sheridan P, Zhang YZ, Nagase R, Horikawa S, Li Z, Matsui H, Kanai A, Saika M, Yamaguchi R, Kozuka-Hata H, Kawabata KC, Yokoyama A, Goyama S, Inaba T, Imoto S, Miyano S, Xu M, Yang FC, Oyama M, Kitamura T.
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Journal Title
Leukemia
Volume: 印刷中
Issue: 6
Pages: 1327-1337
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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