2017 Fiscal Year Final Research Report
The roles of calreticulin in MPN development and normal hematopoiesis.
| Project/Area Number |
15K09480
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Kawasaki Medical School (2016-2017)
University of Miyazaki (2015) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
幣 光太郎 宮崎大学, 医学部, 助教 (20468028)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 骨髄増殖性腫瘍 / Calreticulin |
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| Outline of Final Research Achievements |
We examined the effects of calreticulin (CALR) mutations on myeloproliferative neoplasms (MPNs) development. CALR mutations activated signal transducer and activator of transcription 5 (STAT5) in 293T cells in the presence of thrombopoietin receptor (MPL). Human megakaryocytic cell lines with CALR mutations showed increased growth and acquisition of cytokine-independent growth accompanied by STAT5 phosphorylation. Transgenic mice expressing a human CALR mutation developed ET, with an increase in platelet count, but not hemoglobin level or white blood cell count, in association with an increase in bone marrow mature megakaryocytes. We conclude that the C-terminal of mutant CALR activates JAK-STAT signaling specifically downstream of MPL and may have a crucial role in CALR-induced MPNs.
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| Free Research Field |
血液内科学
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