Maintenance of CML stem cells through regulation of C/EBPbeta transcription factor
Project/Area Number |
25461415
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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 | Kyoto University |
Principal Investigator |
Hirai Hideyo 京都大学, 医学(系)研究科(研究院), 助教 (50315933)
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Co-Investigator(Renkei-kenkyūsha) |
MINAMISHIMA Yoji 慶應義塾大学, 医学部, 講師 (20593966)
MAEKAWA Taira 京都大学, 医学研究科, 教授 (80229286)
YOKOTA Asumi 京都大学, 医学研究科, 研究員 (00571556)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | 白血病幹細胞 / 低酸素 / 転写因子 / 慢性骨髄性白血病 / C/EBPbeta / サイトカイン / 骨髄微小環境 |
Outline of Final Research Achievements |
In order to achieve complete cure of chronic myeloid leukemia (CML), eradication of CML stem cells (CML-SCs) is cruicial. In this study, we focused on hypoxic microenvironment and regulation of the transcription factor C/EBPbeta, which is activated by BCR-ABL and promotes differentiation and exhaustion of CML-SCs. Hypoxic condition in vitro reduced the expression of C/EBPbeta in CML cell lines, and cytokine treatment could not reverse this effect. In contrast, when the mice, which had been transplanted with BCA-ABL expressing bone marrow cells, were treated with cytokines, exhaustion of CML-SCs were promoted via upregulation of C/EBPbeta. These results suggest that cytokine treatment may eradicate CML-SCs by remodeling bone marrow microenvironment including hypoxia in addition to direct action on CML-SCs.
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Report
(4 results)
Research Products
(63 results)
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[Journal Article] Isopentenyl pyrophosphate secreted from zoledronate-stimulated myeloma cells, activates the chemotaxis of γδT cells.2015
Author(s)
Eishi Ashihara, Tatsuya Munaka, Shinya Kimura, Saori Nakagawa, Yoko Nakagawa, Masaki Kanai, Hideyo Hirai, Hirohisa Abe, Takashi Miida, Susumu Yamato, Shuichi Shoji, Taira Maekawa
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Journal Title
Biochem Biophys Res Commun
Volume: 463
Issue: 4
Pages: 650-655
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Isolation of mesenchymal stromal/stem cells from small-volume umbilical cord blood units that do not qualify for the banking system.2015
Author(s)
Yoshioka S, #Miura Y, Iwasa M, Fujishiro A, Yao H, Miura M, Fukuoka M, Nakagawa Y, Yokota A, Hirai H, Ichinohe T, Takaori-Kondo A, Maekawa T (#Corresponding author).
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Journal Title
International Journal of Hematology
Volume: 102
Issue: 2
Pages: 218-229
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] CCAAT/enhancer binding protein beta is dispensable for normal and tumor development in lung.2015
Author(s)
Cai Y, Hirata A, Nakayama S, VanderLaan PA, Levantini E, Yamamoto M, Hirai H, Wong KK, Costa DB, Watanabe H, Kobayashi SS
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Journal Title
Plos ONE
Volume: 10
Issue: 3
Pages: e0120647-e0120647
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] HAX1 in induced pluripotent stem cells from a patient with severe congenital neutropenia improves defective granulopoiesis.2014
Author(s)
Morishima T, Watanabe K, Niwa A, Hirai H, Saida S, Tanaka T, Kato I, Umeda K, Hiramatsu H, Saito MK, Matsubara K, Adachi S, Kobayashi M, Nakahata T, Heike T
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Journal Title
Haematologica
Volume: 99(1)
Issue: 1
Pages: 19-27
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] CCAAT/Enhancer-Binding Protein β Expressed by Bone Marrow Mesenchymal Stromal Cells Regulates Early B-Cell Lymphopoiesis2014
Author(s)
Yoshioka S, Miura Y, Yao H, Satake S, Hayashi Y, Tamura A, Hishita T, Ichinohe T, Hirai H, Takaori-Kondo A, Maekawa T
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Journal Title
Stem Cells
Volume: 32
Issue: 3
Pages: 730-740
DOI
Related Report
Peer Reviewed
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[Journal Article] Loss of SMAD4 from colorectal cancer cells promotes CCL15 expression to recruit CCR1+ myeloid cells and facilitate liver metastasis.2013
Author(s)
Itatani Y, Kawada K, Fujishita T, Kakizaki F, Hirai H, Matsumoto T, Iwamoto M, Inamoto S, Hatano E, Hasegawa S, Maekawa T, Uemoto S, Sakai Y, Taketo MM
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Journal Title
Gastroenterol
Volume: 145(5)
Issue: 5
Pages: 1064-1075
DOI
NAID
Related Report
Peer Reviewed
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[Journal Article] Myeloid-Derived Suppressor Cells Play Crucial Roles in the Regulation of Mouse Collagen-Induced Arthritis.2013
Author(s)
1. Fujii W, Ashihara E, Hirai H, Nagahara H, Kajitani N, Fujioka K, Murakami K, Seno T, Yamamoto A, Ishino H, Kohno M, Maekawa T, Kawahito Y.
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Journal Title
J Immunol
Volume: 191
Issue: 3
Pages: 1073-1081
DOI
Related Report
Peer Reviewed
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[Presentation] C/EBPβ Isoforms Distinctively and Collaboratively Regulate the Behavior of Hematopoietic Stem and Progenitor Cells in Regenerative Conditions2015
Author(s)
Sato A, Hirai H, Yokota A, Tamura A, Shoji T, Kashiwagi T, Iwasa M, Fujishiro A, Miura Y, Maekawa T
Organizer
American Society of Hematology, 57th Annual Meeting
Place of Presentation
Orlando, USA
Year and Date
2015-12-07
Related Report
Int'l Joint Research
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[Presentation] Csf1r Is a Downstream Target of C/EBPβ in Ly6C¯ Monocytes.2015
Author(s)
Tamura A, Hirai H, Yokota A, Sato A, Shoji T, Kashiwagi T, Iwasa M, Fujishiro A, Miura Y, Maekawa T
Organizer
American Society of Hematology, 57th Annual Meeting
Place of Presentation
Orlando, USA
Year and Date
2015-12-05
Related Report
Int'l Joint Research
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[Presentation] IFNα promotes differentiation of BCR-ABL+ leukemic cells through upregulating C/EBPβ.2015
Author(s)
Yokota A, Hirai H, Hayashi Y, Tamura A, Sato A, Iwasa M, Fujishiro A, Shoji T, Miura Y, Maekawa T
Organizer
International Society for Experimental Hematology, 44th Annual Scientific Meeting
Place of Presentation
Kyoto
Year and Date
2015-09-17
Related Report
Int'l Joint Research
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[Presentation] Effects of Irradiation on the Functional Characteristics of Human Bone Marrow Mesenchymal Stromal/Stem Cells.2014
Author(s)
Masaki Iwasa, Yasuo Miura, Aya Fujishiro, Akihiro Tamura, Atsushi Sato, Asumi Yokota, Yoko Nakagawa, Satoshi Yoshioka, Hideyo Hirai, Akira Andoh, Tatsuo Ichinohe and Taira Maekawa
Organizer
The 56th ASH Annual Meeting
Place of Presentation
San Francisco (USA)
Year and Date
2014-12-06 – 2014-12-09
Related Report
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[Presentation] Effect of irradiation on the characteristics of human bone marrow mesenchymal stromal/stem cells.2014
Author(s)
Iwasa M, Miura Y, Yao H, Yoshioka S, Fujishiro A, Tamura A, Sato A, Yokota A, Hirai H, Ando A, Ichinohe T, Maekawa T
Organizer
第76回日本血液学会学術総会
Place of Presentation
大阪国際会議場(大阪)
Year and Date
2014-11-01
Related Report
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[Presentation] Isolation of mesenchymal stromal/stem cells from UCB ineligible for public UCB donation.2014
Author(s)
Yoshioka S, Miura Y, Yao H, Iwasa M, Fujishiro A, Higashi Y, Yokota A, Tamura A, Sato A, Hirai H, Ichinohe T, Takaori-Kondo A, Maekawa T
Organizer
第76回日本血液学会学術総会
Place of Presentation
大阪国際会議場(大阪)
Year and Date
2014-11-01
Related Report
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[Presentation] Protective roles of myeloid-derived suppressor cells in autoimmune arthritis murine models through inhibiting pro-inflammatory immune response of CD4+ T cell.
Author(s)
Fujii W, Nagahara H, Kajitani N, Fujioka K, Murakami K, Nakamura K, Seno T, Yamamoto A, Ishino H, Kohno M, Kawahito Y
Organizer
The 57th Annual General Assemble and Scientific Meeting of the Japan Collage of Rheumatology
Place of Presentation
京都
Related Report
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[Presentation] Myeloid-derived suppressor cells have regulatory roles in mouse collagen-induced arthritis.
Author(s)
Fujii W, Ashihara E, Hirai H, Nagahara H, Fujioka K, Murakami K, Seno T, Yamamoto A, Ishino H, Kohno M, Maekawa T, Kawahito Y
Organizer
Annual European Congress of Rheumatology
Place of Presentation
Madrid, Spain
Related Report
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[Presentation] C/EBPβ expressed by bone marrow mesenchymal stromal cells is indispensable for precursor B-cell lymphopoiesis.
Author(s)
Yoshioka S, Miura Y, Yao H, Iwasa M, Sato A, Tamura A, Yokota A, Hishita T, Ichinohe T, Hirai H, Maekawa T
Organizer
American Society of Hematology, 55th Annual Meeting
Place of Presentation
New Orleans, LA, USA
Related Report
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[Presentation] Cytokine-STATs signalings upregulate endogenous C/EBPβ in BCR-ABL+ leukemic cells independently from BCR-ABL signaling.
Author(s)
Yokota A, Hirai H, Hayashi Y, Tamura A, Sato A, Yao H, Yoshioka S, Iwasa M, Ashihara E, Miura Y, Maekawa T
Organizer
American Society of Hematology, 55th Annual Meeting
Place of Presentation
New Orleans, LA, USA, December 7, 2013
Related Report
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[Presentation] Cell-intrinsic and -extrinsic involvement of C/EBPβ in the regulation of hematopoietic stem cells.
Author(s)
Tamura A, Hirai H, Hayashi Y, Yokota A, Sato A, Yao H, Yoshioka S, Iwasa M, Ashihara E, Miura Y, Maekawa T
Organizer
American Society of Hematology, 55th Annual Meeting
Place of Presentation
New Orleans, LA, USA
Related Report
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[Presentation] Hypoxia-Adapted Myeloma Cells Possess Stem Cell Character.
Author(s)
Ashihara E, Nakagawa Y, Yao H, Yokota A, Miura Y, Takata K, Kitamura Y, Hirai H , Maekawa T
Organizer
American Society of Hematology, 55th Annual Meeting
Place of Presentation
New Orleans, LA, USA
Related Report
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[Presentation] Direct Interaction with Bone Marrow Mesenchymal Stromal/Stem Cells Is Required for Hematopoietic Expansion by Parathyroid Hormone.
Author(s)
Yao H, Miura Y, Yoshioka S, Iwasa M, Sato A, Tamura A, Yokota A, Ashihara E, Ichinohe T, Hirai H,Maekawa T
Organizer
American Society of Hematology, 55th Annual Meeting
Place of Presentation
New Orleans, LA, USA
Related Report
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[Presentation] Proliferation and differentiation of hematopoietic cells by osteogenic-induced bone marrow MSCs.
Author(s)
Yao H, Miura Y, Yoshioka S, Iwasa M, Sato A, Hayashi Y, Tamura A, Yokota A, Ichinohe T, Tohyama K, Hirai H, Maekawa T
Organizer
The 75th Annual Meeting of the Japanese Society of Hematology
Place of Presentation
札幌
Related Report
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[Presentation] Involvement of C/EBPβ in the regulation of hematopoietic stem cells.
Author(s)
Tamura A, Hirai H, Hayashi Y, Yokota A, Yao H, Yoshioka S, Sato A, Iwasa M, Ashihara E, Miura Y, and Maekawa T
Organizer
The 75th Annual Meeting of the Japanese Society of Hematology
Place of Presentation
札幌
Related Report
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