Establishment of in vitro model for essential thrombocythemia by mutant calreticulin
Project/Area Number |
16K19587
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Research Category |
Grant-in-Aid for Young Scientists (B)
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Allocation Type | Multi-year Fund |
Research Field |
Hematology
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Research Institution | Juntendo University |
Principal Investigator |
MIZUKAMI Yoshihisa 順天堂大学, 医学(系)研究科(研究院), 博士研究員 (30756698)
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Research Collaborator |
Komatsu Norio 順天堂大学, 医学部, 血液学講座 (50186798)
Araki Marito 順天堂大学, 医学部 輸血・幹細胞制御学, 准教授 (80613843)
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Project Period (FY) |
2016-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2016: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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Keywords | 骨髄増殖性腫瘍 / calreticulin / JAK2 / ドライバー変異 / 骨髄線維症 / 本態性血小板血症 / iPS細胞 / 造血幹細胞 / カルレティキュリン / 奇形腫 / 変異型CALR / 免疫不全マウス / 原発性骨髄線維症 / 疾患iPS細胞 |
Outline of Final Research Achievements |
Somatic mutations in the calreticulin (CALR) gene have been found in most patients with myeloproliferative neoplasms (MPNs). Mutant CALR activates the thrombopoietin receptor, which promote the development of MPNs. However, the roles of mutant CALR in human hematopoietic cell differentiation remain unknown. To examine the effect of mutant CALR on hematopoietic cell differentiation, we generated induced pluripotent stem cells from an essential thrombocythaemia (ET) patient with CALR mutation. Megakaryopoiesis was observed in hematopoietic progenitor cells with mutant CALR rather than in healthy ones, suggesting that the system recapitulates megakaryocytosis occurred in the bone marrow of CALR-mutant ET patients. We established an in vitro model system that recapitulates megakaryopoiesis caused by mutant CALR. This system can be used to validate therapeutic compounds for MPN patients with CALR mutations and in detailed studies on mutant CALR in human hematological cell differentiation.
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Report
(3 results)
Research Products
(11 results)
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[Journal Article] Skewed megakaryopoiesis in human iPS cell-derived hematopoietic progenitor cells harboring calreticulin mutations2018
Author(s)
Hiraku Takei, Yoko Edahiro, Shuichi Mano, Nami Masubuchi, Yoshihisa Mizukami, Misa Imai, Soji Morishita, Satoshi Tsuneda, Hiroshi Endo, Sou Nakamura, Koji Eto, Akimichi Ohsaka, Marito Araki, Norio Komatsu
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Journal Title
British Journal of Haematology
Volume: 印刷中
Related Report
Peer Reviewed / Open Access
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[Presentation] Skewed megakaryopoiesis observed in hematopoietic progenitor cells harboring calreticulin mutation.2017
Author(s)
Takei H, Mano S, Masubuchi N, Mizukami Y, Morishita S, Imai M, Edahiro Y, Hironaka Y, Nudejima M, Tsuneda S, Endo H, Nakamura S, Eto K, Ohsaka A, Araki M, Komatsu N.
Organizer
2017年度 生命科学系学会合同年次大会
Related Report
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[Presentation] Skewed megakaryopoiesis by mutant calreticulin is associated with increased GATA2 expression.2017
Author(s)
Takei H, Mano S, Masubuchi N, Mizukami Y, Imai M, Morishita S, Edahiro Y, Hironaka Y, Nudejima M, Tsuneda S, Endo H, Nakamura S, Eto K, Ohsaka A, Araki M, Komatsu N.
Organizer
第79回日本血液学会学術集会
Related Report
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[Presentation] Establishment of an in vitro model for the skewed megakaryopoiesis by calreticulin mutation in human cells.2017
Author(s)
Takei H, Mano S, Masubuchi N, Mizukami Y, Morishita S, Imai M, Edahiro Y, Hironaka Y, Nudejima M, Tsuneda S, Endo H, Nakamura S, Eto K, Ohsaka A, Araki M, Komatsu N
Organizer
22nd Congress European Hematology Association
Related Report
Int'l Joint Research
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[Presentation] Engagement of mutant calreticulin and MPL in a cellular compartment is required for MPL activation.2017
Author(s)
Nami Masubuchi, Marito Araki, Erina Hayashi, Yinjie Yang, Misa Imai, Yoshihisa Mizukami, Yumi Hironaka, Hiraku Takei, Soji Morishita, Yoshihiko Kihara, Yoko Edahiro, Akimichi Ohsaka, Norio Komatsu
Organizer
第79回日本血液学会学術集会
Related Report
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[Presentation] 家族性骨髄増殖性腫瘍患者からの iPS 細胞株の樹立.2017
Author(s)
眞野修一, 竹井拓, 森下総司, 水上喜久, 増渕菜弥, 弘中由美, 橳島麻衣 ,常田 聡, 大坂顯通, 荒木真理人, 小松則夫
Organizer
第 79 回日本血液学会学術集会
Related Report
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[Presentation] Modeling MPN phenotypes in vitro by using iPSC harboring CALR ins5 mutation,2016
Author(s)
Takei H, Masubuchi N, Mano S, Araki M, Morishita S, Mizukami Y, Kan S, Edahiro Y, Sunami Y, Hironaka Y, Endo H, Nakamura S, Eto K, Osaka A, Komatsu N
Organizer
第78回日本血液学会
Place of Presentation
横浜
Year and Date
2016-10-13
Related Report
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[Presentation] Mutant calreticulin activate the thrombopoietin receptor in myeloproliferative neoplasm2016
Author(s)
Araki M, Yang Y, Masubuchi N, Hironaka Y, Takei H, Morishita S, Mizukami Y, Kan S, Shirane S, Edahiro Y, Sunami Y, Ohsaka A, Komatsu N.
Organizer
第78回日本血液学会
Place of Presentation
横浜
Year and Date
2016-10-13
Related Report
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[Presentation] Activation of the thrombopoietin receptor by mutant calreticulin in CALR-mutant myeloproliferative neoplasms2016
Author(s)
Araki M, Yang Y, Masubuchi N, Hironaka Y, Takei H, Morishita S, Mizukami Y, Kan S, Shirane S, Edahiro Y, Sunami Y, Ohsaka A, Komatsu N
Organizer
21st Congress European hematology association
Place of Presentation
Copenhagen
Year and Date
2016-06-09
Related Report
Int'l Joint Research