Targeting cancer stem cells in chronic myeloid neoplasms
Project/Area Number |
26461424
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Hematology
|
Research Institution | Kyushu University |
Principal Investigator |
|
Project Period (FY) |
2014-04-01 – 2017-03-31
|
Project Status |
Completed (Fiscal Year 2016)
|
Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | 骨髄増殖性腫瘍 / 骨髄異形成症候群 / がん幹細胞 / 免疫不全マウス / SIRPA / Kit変異 / 幹細胞アッセイシステム / 異種移植モデル |
Outline of Final Research Achievements |
Cancer stem cells (CSCs) are therapeutic targets and must be eliminated to cure the patients. Howerver ,those cells have not been found yet in MDS/MPN. Immunodeficient mice are widely used to reconstitute human normal hematopoiesis and acute leukemia. Howerever, in these models, significant reconstitution of human erythroid and megakaryocyte lineages has been difficult to achieve. Here, we show that introduction of homozygous KitWv mutation (K) into the C57BL/6.Rag2(null)Il2rg(null) mice with NOD-Sirpa (BRGS) strongly promoted human multilineage reconstitution. The new BRGSK mice showed significantly higher levels of human cell chimerism and myeloid reconstitution for a long-term, as compared to BRGS mice. Strikingly, BRGSK mice displayed robust reconstitution of human erythropoiesis and thrombopoiesis with terminal maturation in the bone marrow.This new xenograft model should be a strong tool to study human hematopoiesis including erythropoiesis and thrombopoiesis.
|
Report
(4 results)
Research Products
(11 results)
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[Journal Article] Clinical features and outcomes of patients with primary myelofibrosis in Japan: report of a 17-year nationwide survey by the Idiopathic Disorders of Hematopoietic Organs Research Committee of Japan.2017
Author(s)
Takenaka K, Shimoda K, Uchida N, Shimomura T, Nagafuji K, Kondo T, Shibayama H, Mori T, Usuki K, Azuma T, Tsutsumi Y, Tanaka J, Dairaku H, Matsuo K, Ozawa K, Kurokawa M, Arai S, Akashi K.
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Journal Title
Int J Henatol
Volume: 105
Issue: 1
Pages: 59-69
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Enhanced Reconstitution of Human Erythropoiesis and Thrombopoiesis in an Immunodeficient Mouse Model with Kit(Wv) Mutations.2016
Author(s)
A. Yurino, K. Takenaka, T. Yamauchi, T. Nunomura, Y. Uehara, F. Jinnouchi, K. Miyawaki, Y. Kikushige, K. Kato, T. Miyamoto, H. Iwasaki, Y. Kunisaki, *K. Akashi
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Journal Title
Stem Cell Reports
Volume: 7
Issue: 3
Pages: 425-438
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Calreticulin mutation does not contribute to disease progression in essential thrombocythemia by inhibiting phagocytosis.2016
Author(s)
S. Daitoku, K. Takenaka, T. Yamauchi, A. Yurino, F. Jinnouchi, T. Nunomura, T. Eto, T. Kamimura, M. Higuchi, N. Harada, N. Saito, T. Miyamoto, H. Iwasaki, *K. Akashi
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Journal Title
Exp Hematol
Volume: 44
Issue: 9
Pages: 817-825
DOI
Related Report
Peer Reviewed
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[Journal Article] A TIM-3/Gal-9 Autocrine Stimulatory Loop Drives Self-Renewal of Human Myeloid Leukemia Stem Cells and Leukemic Progression.2015
Author(s)
Kikushige Y, Miyamoto T, Yuda J, Jabbarzadeh-Tabrizi S, Shima T, Takayanagi S, Niiro H, Yurino A, Miyawaki K, Takenaka K, Iwasaki H, Akashi K
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Journal Title
Cell Stem Cell.
Volume: 17
Issue: 3
Pages: 341-352
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] A multinational, open-label, phase 2 study of ruxolitinib in Asian patients with myelofibrosis: Japanese subset analysis.2015
Author(s)
Oritani K, Okamoto S, Tauchi T, Saito S, Ohishi K, Handa H, Takenaka K, Gopalakrishna P, Amagasaki T, Ito K, Akashi K.
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Journal Title
Int J Hematol
Volume: 101
Issue: 3
Pages: 295-304
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] CD41 marks the initial myelo-erythroid lineage specification in adult mouse hematopoiesis: redefinition of murine common myeloid progenitor.2015
Author(s)
Miyawaki K, Arinobu Y, Iwasaki H, Kohno K, Tsuzuki H, Iino T, Shima T, Kikushige Y, Takenaka K, Miyamoto T, Akashi K.
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Journal Title
Stem Cells
Volume: 33
Issue: 3
Pages: 976-87
DOI
Related Report
Peer Reviewed
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[Journal Article] Efficacy and safety of ruxolitinib in Asian patients with myelofibrosis.2015
Author(s)
Jung CW, Shih LY, Xiao Z, Jie J, Hou HA, Du X, Wang MC, Park S, Eom KS, Oritani K, Okamoto S, Tauchi T, Kim JS, Zhou D, Saito S, Li J, Handa H, Jianyong L, Ohishi K, Hou M, Depei W, Takenaka K, Liu T, Hu Y, Amagasaki T, Ito K, Gopalakrishna P, Akashi K.
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Journal Title
Leuk Lymphoma
Volume: 56
Issue: 7
Pages: 2067-2074
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] The ordered acquisition of Class II and Class I mutations directs formation of human t(8;21) acute myelogenous leukemia stem cell.2014
Author(s)
Shima T, Miyamoto T, Kikushige Y, Yuda J, Tochigi T, Yoshimoto G, Kato K, Takenaka K, Iwasaki H, Mizuno S, Goto N, Akashi K.
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Journal Title
Exp. Hematol.
Volume: 42
Issue: 11
Pages: 955-65
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Introduction of Macrophage Tolerance By Human SIRPA Knock-in Enhances Peripheral Reconstitution of Human Hematopoiesis in Xenotransplantation Model2016
Author(s)
Jinnnouchi F, Takenaka K, Iwamoto C, Yamauchi T, Yurino A, Nunomura T, Kikushige Y, Kato K, Miyamoto T, Akashi K
Organizer
the 58th of annual meeting of American Society of Hematology
Place of Presentation
San Diego, CA
Year and Date
2016-12-03
Related Report
Int'l Joint Research
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