The role of mutant Calreticulin and HMGA2 in myeloproliferative neoplasms
Project/Area Number |
15K09483
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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 | Fukushima Medical University |
Principal Investigator |
Ogawa Kazuei 福島県立医科大学, 医学部, 教授 (40423800)
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Co-Investigator(Kenkyū-buntansha) |
植田 航希 福島県立医科大学, 医学部, 助教 (80632190)
池田 和彦 福島県立医科大学, 医学部, 准教授 (90381392)
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Project Period (FY) |
2015-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
Keywords | MPN / CALR / 骨髄増殖性腫瘍 / ドライバー変異 / HMGA2 |
Outline of Final Research Achievements |
Myeloproliferative neoplasms (MPNs) are a group of diseases in which mature hematopoietic cells proliferate. Recently, insertion/deletion mutations in exon 9 of Calreticulin (CALR) were discovered in MPNs. However, the role of the mutant CALR in MPN hematopoiesis are largely unknown. Thus, we generated 2 types of mice with mutant Calr; type 1-like 10 bp deletion (CR10d) and type 2-like 2 bp insertion (CR2i) using genetic modification by CRISPER/Cas9 method. Both mice mimicked mutations in patients with MPN. CR2i mice showed increased spleen weight per body weight and a reduced bone marrow T cell ratio compared with wild-type mice. Both CR10d and CR2i mice showed increased bone marrow myeloid cells. We are studying the effect of the Calr mutants on hematopoietic stem cell and progenitor function by BM transplant experiments and progenitor assays. In addition, we will generate Hmga2+CR10d and Hmga2+CR2i mice by crossing Hmga2-transgenic mice and mice with mutant Calr.
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Report
(4 results)
Research Products
(10 results)
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[Journal Article] The Amelioration of Myelofibrosis with Thrombocytopenia by a JAK1/2 Inhibitor, Ruxolitinib, in a Post-polycythemia Vera Myelofibrosis Patient with a <i>JAK2</i> Exon 12 Mutation2017
Author(s)
Kazuhiko Ikeda, Koki Ueda, Takahiro Sano, Kazuei Ogawa, Takayuki Ikezoe, Yuko Hashimoto, Soji Morishita, Norio Komatsu, Hitoshi Ohto, Yasuchika Takeishi
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Journal Title
Internal Medicine
Volume: 56
Issue: 13
Pages: 1705-1710
DOI
NAID
ISSN
0918-2918, 1349-7235
Related Report
Peer Reviewed / Open Access
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[Journal Article] Hmga2 collaborates with JAK2 V617F in the development of myeloproliferative neoplasms2017
Author(s)
Ueda K, Ikeda K, Ikezoe T, Harada-Shirado K, Ogawa K, Hashimoto Y, Sano T, Ohkawara H, Kimura S, Shichishima-Nakamura A, Nakamura Y, Shikama Y, Mori T, Mason PJ, Bessler M, Morishita S, Komatsu N, Shide K, Shimoda K, Koide S, Aoyama K, Oshima M, Iwama Aand Takeishi Y.
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Journal Title
Blood Advances
Volume: 1
Issue: 15
Pages: 1001-1015
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Autocrine and Paracrine Interactions between Multiple Myeloma Cells and Bone Marrow Stromal Cells by Growth Arrest-specific Gene 6 Cross-talk with Interleukin-6.2017
Author(s)
Furukawa M, Ohkawara H, Ogawa K, Ikeda K, Ueda K, Shichishima-Nakamura A, Ito E, Imai JI, Yanagisawa Y, Honma R, Watanabe S, Waguri S, Ikezoe T, Takeishi Y
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Journal Title
The Journal of biological chemistry
Volume: 292
Issue: 10
Pages: 4280-4292
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Steroid-resistant autoimmune myelofibrosis in a patient with autoimmune hepatitis and Evans syndrome complicated with increased expression of TGF-β in the bone marrow: a case report2017
Author(s)
Hiroshi Ohkawara, Miki Furukawa, Kazuhiko Ikeda, Akiko Shichishima-Nakamura, Masahiko Fukatsu, Takahiro Sano, Koki Ueda, Satoshi Kimura, Risa Kanai, Yuka Oka, Fumi Murakami, Osamu Suzuki, Yuko Hashimoto, Kazuei Ogawa, Takayuki Ikezoe
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Journal Title
International Journal of Hematology
Volume: 106
Issue: 5
Pages: 718-724
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Reduction of c-Fos via Overexpression of miR-34a Results in Enhancement of TNF- Production by LPS in Neutrophils from Myelodysplastic Syndrome Patients.2016
Author(s)
Shikama Y, Cao M, Ono T, Feng X, Noji H, Kimura H, Ogawa K, Suzuki Y, Ikeda K, Takeishi Y, Kimura J.
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Journal Title
PLoS One
Volume: 11
Issue: 8
Pages: e0158527-e0158527
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] HMGA2 orchestrates the tumorgenesis of myeloproliferative neoplasms (MPN) in corporation with JAK2V617F.2016
Author(s)
Ueda K, Ikeda K, Ikezoe T, Ogawa K, Hashimoto Y, Harada-Shirado K, Ohkawara H, Komatsu N, Shide K, Shimoda K, Koide S, Oshima M, Iwama A, Takeishi Y.
Organizer
American Society of Hematology
Place of Presentation
San Diego, USA
Year and Date
2016-12-03
Related Report
Int'l Joint Research
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