Genome editing in human hematopoietic cells for the understanding of leukemogenesis
Project/Area Number |
15K09478
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
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Research Institution | Kumamoto University |
Principal Investigator |
MATSUI HIROTAKA 熊本大学, 大学院生命科学研究部(医), 教授 (60379849)
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Research Collaborator |
SHINRIKI Satoru 熊本大学, 大学院生命科学研究部, 准教授
NAGAMACHI Akiko 広島大学, 原爆放射線医科学研究所, 助教
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
|
Keywords | ゲノム編集 / 急性骨髄性白血病 / 骨髄異形成症候群 / DDX41 / DDX41遺伝子 / DNAメチル化 / 造血器腫瘍 / エピゲノム |
Outline of Final Research Achievements |
To elucidate the pathogenesis of hematopoietic tumors caused by gene mutations or deletions, we applied genome editing for leukemia cell lines and cord blood-derived CD34 positive hematopoietic progenitor cells. In this study, we targeted the DDX41, where germ line as well as somatic mutations are observed at a certain rate, for gene editing. We previously revealed that DDX41 protein plays a role in the processing of pre-ribosomal RNA, however, its physiological function and the role of its mutant for leukemogenesis has not been elucidated so far. We found that a leukemia cell line that does not express DDX41, established using CRISPR/CAS9 system, showed growth inhibition as compared with control cells. We assume this was caused by the inhibition of ribosome biogenesis, and further studies using these cells are underway.
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Report
(4 results)
Research Products
(50 results)
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[Journal Article] A novel ASXL1-OGT axis plays roles in H3K4 methylation and tumor suppression in myeloid malignancies.2018
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 K, 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: in press
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Loss of CYLD promotes cell invasion via ALK5 stabilization in oral squamous cell carcinoma2018
Author(s)
Shinriki S, Jono H, Maeshiro M, Nakamura T, Guo J, Li JD, Ueda M, Yoshida R, Shinohara M, Nakayama H, Matsui H, Ando Y.
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Journal Title
Journal of Pathology
Volume: 244
Issue: 3
Pages: 367-379
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Genetic and clinical characteristics of hereditary transthyretin amyloidosis in endemic and non-endemic areas: experience from a single-referral center in Japan.2018
Author(s)
Yamashita T, Ueda M, Misumi Y, Masuda T, Nomura T, Tasaki M, Takamatsu K, Sasada K, Obayashi K, Matsui H, Ando Y.
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Journal Title
Journal of Neurology
Volume: 265
Issue: 1
Pages: 134-140
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A case of pulmonary thromboembolism due to coagulation factor V Leiden in Japan ~Usefulness of next generation sequencing~.2017
Author(s)
Sueta D, Ito M, Uchiba M, Sakamoto K, Yamamoto E, Izumiya Y, Kojima S, Kaikita K, Shinriki S, Hokimoto S, Matsui H, Tsujita K.
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Journal Title
Thromb. J
Volume: in press
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inflammatory state exists in familial amyloid polyneuropathy that may be triggered by mutated transthyretin.2017
Author(s)
Suenaga G, Ikeda T, Masuda T, Motokawa H, Yamashita T, Takamatsu K, Misumi Y, Ueda M, Matsui H, Senju S, Ando Y.
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Journal Title
Sci. Rep
Volume: 7(1)
Issue: 1
Pages: 1579-2017
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A novel LSD1 inhibitor NCD38 ameliorates MDS-related leukemia with complex karyotype by attenuating leukemia programs via activating super-enhancers.2017
Author(s)
Sugino N, Kawahara M, Tatsumi G, Kanai A, Matsui H, Yamamoto R, Nagai Y, Fujii S, Shimazu Y, Hishizawa M, Inaba T, Andoh A, Suzuki T, Takaori-Kondo A.
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Journal Title
Leukemia
Volume: in press
Issue: 11
Pages: 2303-2314
DOI
Related Report
Peer Reviewed
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[Journal Article] 実践精度管理2017
Author(s)
池田勝義, 山内露子, 西村仁志, 山下昭一郎, 早原千恵, 松井啓隆
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Journal Title
日本臨床検査自動化学会会誌
Volume: 42(2)
Pages: 123-134
Related Report
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[Journal Article] Impact of combinatorial dysfunctions of Tet2 and Ezh2 on the epigenome in the pathogenesis of myelodysplastic syndrome.2016
Author(s)
Hasegawa N, Oshima M, Sashida G, Matsui H, Koide S, Saraya A, Wang C, Muto T, Takane K, Kaneda A, Shimoda K, Nakaseko C, Yokote K, Iwama A.
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Journal Title
Leukemia
Volume: in press
Issue: 4
Pages: 861-871
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Propagation of tri-methylated H3K27 regulated by EED is required for embryogenesis, hematopoietic maintenance, and tumor suppression.2016
Author(s)
Ueda T, Nakata Y, Nagamachi A, Yamasaki N, Kanai A, Matsui H, Honda ZI, Oda H, Wolff L, Inaba T, Honda H.
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Journal Title
PNAS
Volume: 113(37)
Issue: 37
Pages: 10370-10375
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Hereditary amyloidosis with cardiomyopathy caused by the novel variant transthyretin A36D.2016
Author(s)
Yamashita T, Ueda M, Saga N, Nanto K, Tasaki M, Masuda T, Misumi Y, Oda S, Fujimoto A, Amano T, Takamatsu K, Yamashita S, Obayashi K, Matsui H, Ando Y.
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Journal Title
Amyloid
Volume: in press
Issue: 3
Pages: 207-208
DOI
Related Report
Peer Reviewed
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[Journal Article] A new variant of acute promyelocytic leukemia with IRF2BP2-RARA fusion.2016
Author(s)
Shimomura Y, Mitsui H, Yamashita Y, Kamae T, Kanai A, Matsui H, Ishibashi T, Tanimura A, Shibayama H, Oritani K, Kuyama J, Kanakura Y.
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Journal Title
Cancer Sci.
Volume: 107(8)
Issue: 8
Pages: 1165-1168
DOI
Related Report
Peer Reviewed
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[Journal Article] Biological implication of somatic DDX41 p.R525H mutation in acute myeloid leukemia.2016
Author(s)
Kadono M, Kanai A, Nagamachi A, Shinriki S, Kawata J, Iwato K, Kyo T, Oshima K, Yokoyama A, Kawamura T, Nagase R, Inoue D, Kitamura T, Inaba T, Ichinohe T, Matsui H.
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Journal Title
Exp. Hematol.
Volume: 44(8)
Issue: 8
Pages: 745-754
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Setdb1 maintains hematopoietic stem and progenitor cells by restricting the ectopic activation of non-hematopoietic genes.2016
Author(s)
Koide S, Oshima M, Takubo K, Yamazaki S, Nitta E, Saraya A, Aoyama K, Kato Y, Miyagi S, Nakajima-Takagi Y, Chiba T, Matsui H, Arai F, Suzuki Y, Kimura H, Nakauchi H, Suda T, Shinkai Y,Iwama A.
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Journal Title
Blood
Volume: 128(5)
Issue: 5
Pages: 638-649
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Fbxl10 overexpression in murine hematopoietic stem cells induces leukemia involving metabolic activation and upregulation of Nsg2.2015
Author(s)
Ueda T, Nagamachi A, Takubo K, Yamasaki N, Matsui H, Kanai A, Nakata Y, Ikeda K, Konuma T, Oda H, Wolff L, Honda Z, Wu X, Helin K, Iwama A, Suda T, Inaba T, Honda H
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Journal Title
Blood
Volume: 125
Pages: 3437-3446
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] Emergence of resistant variants detected by ultra-deep sequencing after asunaprevir and daclatasvir combination therapy in patients infected with hepatitis C virus genotype 1.2015
Author(s)
Kosaka K, Imamura M, Hayes CN, Abe H, Hiraga N, Yoshimi S, Murakami E, Kawaoka T, Tsuge M, Aikata H, Miki D, Ochi H, Matsui H, Kanai A, Inaba T, Chayama K
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Journal Title
J Viral Hepat
Volume: 22
Pages: 158-165
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] SETBP1 mutations drive leukemic transformation in ASXL1-mutated MDS.2015
Author(s)
Inoue D, Kitaura J, Matsui H, Hou HA, Chou WC, Nagamachi A, Kawabata KC, Togami K, Nagase R, Horikawa S, Saika M, Micol JB, Hayashi Y, Harada Y, Harada H, Inaba T, Tien HF, Abdel-Wahab O, Kitamura T.
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Journal Title
Leukemia
Volume: 29
Pages: 847-857
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
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[Presentation] 血液培養よりHelicobacter cinaediを分離した5症例の検討 (YIAシンポジウム)2017
Author(s)
荻 泰裕, 山本 景一, 吉永 浩子, 土橋 紗央里, 福嶋 理香, 大隈 雅紀, 池田 勝義, 富田 純子, 河村 好章, 馬場 秀夫, 松井 啓隆
Organizer
第57回日本臨床化学会年次学術集会
Related Report
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[Presentation] 当院における安全な輸血療法の為の取り組み 院内輸血ラウンドをとおして2017
Author(s)
石原 綾子, 福吉 葉子, 米村 雄士, 有山 朝子, 吉田 朝子, 下山 治香, 井上 有子, 富永 るみ子, 齋藤 寿子, 眞鳥 千晶, 森川 由梨, 池田 勝義, 内場 光浩, 松井 啓隆
Organizer
第65回日本輸血細胞治療学会総会
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