| Project/Area Number |
23650603
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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 |
Tumor biology
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
GOTOU Akihiko 東京医科大学, 医学部, 講師 (00297293)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 急性前骨髄性白血病 / CXCL12 / CXCR4 / 走化性 / all-trans retinoic acid / CXCR7 / phospholipaseC / ATRA |
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| Research Abstract |
Differentiation-induction therapy with all trans retinoic acid (ATRA) is the first line therapy in acute promyelocytic leukemia (APL). Differentiation syndrome (DS) is the most serious adverse event during ATRA therapy. Further, although mobilization of APL cells into peripheral blood requires additional chemotherapy during ATRA therapy, the mechanism of the mobilization is unclear. In the current study, CXCL12 appeared to be a chemoattractant of APL cells. Treatment of APL cells with ATRA enhanced chmotaxis towards CXCL12. Increase of chemotaxis significantly associated with occurrence of DS and the requirement of additional chemotherapy. Activation of phospholipase C pathway appeared to be crucial for the chemotaxis. These results suggest that chomotaxis ability of APL cells toward CXCL12 is involved in the pathogenesis of DS and the requirement of chemotherapy during induction therapy with ATRA. Furthermore, specific signal targeted-therapy might contribute to prevent DS and additional chemotherapy.
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