| Project/Area Number |
26670186
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Experimental pathology
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| Research Institution | Kobe University (2016)
Tokyo Medical and Dental University (2014-2015) |
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Principal Investigator |
Abe Shiho 神戸大学, 医学部附属病院, 特命助教 (30632111)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 造血幹細胞ニッチ / 骨髄異形成症候群 / CXCL12 / アポトーシス |
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| Outline of Final Research Achievements |
We analyzed the association between the CXCL12(+) stromal cells and CD34(+) tumor cells of myelodysplastic syndromes (MDS). In MDS bone marrow, CXCL12(+) cell density was higher than control bone marrow. The CXCL12(+) cells were in contact with CD34(+) tumor cells, which were positive for several anti-apoptotic markers. Furthermore, CXCL12-high MDS cases had the greater tendency to show rapid disease progression than CXCL12-low cases. In vitro analysis, MDS-derived hematopoietic cell line cells cocultured with CXCL12(+) stromal cell line cells showed upregulation of anti-apoptotic molecules and drug-resistance for Ara-C treatment. These phenomena were inhibited by CXCR4 antagonist, AMD3100, therefore CXCL12-CXCR4 signaling was essential for the interaction between MDS cells and CXCL12(+) stromal cells. Thus, CXCL12(+) stromal cells may represent a novel MDS therapeutic target.
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