Elucidation of the mechanism of transformation of myeloproliferative neoplasm into acute myelogenous leukemia for novel therapeutic strategy for the disease.
| Project/Area Number |
25893047
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
KAGOYA YUKI 東京大学, 医学部附属病院, 助教 (70706960)
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| Project Period (FY) |
2013-08-30 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 骨髄増殖性腫瘍 / 急性骨髄性白血病 / JAK2V617F遺伝子変異 / リポカリン-2 / DNA損傷 / p53 / 活性酸素 / JAK2V617F変異 / ｐ５３ / JAK2V617F / 鉄過剰 |
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| Outline of Final Research Achievements |
In the present study, we aimed to elucidate the pathogenesis of myeloproliferative neoplasm (MPN), one of the major hematological malignancies. We focused on JAK2V617F mutation frequently seen in MPN and analyzed its contribution to the incidence of MPN and the transformation of MPN into acute myelogenous leukemia (AML). We found that MPN cells abundantly secreted lipocalin-2. First, lipocalin-2 induced DNA damage in the neightbouring normal hematopoietic cells within MPN bone marrow in a paracrine manner, which could contribute to the progression of MPN into AML through accumulation of the genetic mutation. Moreover, we showed that lipocalin-2 suppressed normal hematopoiesis through inducing the DNA damage-induced apoptosis. Since proliferation of MPN clones were not affected by lipocalin-2, lipocalin-2 secretion resulted in the relative growth advantage of MPN clones over normal hematopoietic cells, which promoted the development of MPN.
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Report
(3 results)
Research Products
(4 results)
