2013 Fiscal Year Final Research Report
Overcoming resistance and pharmacologicaly-directed tailor-made chemotherapy for leukemia
| Project/Area Number |
23501307
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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 |
Clinical oncology
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| Research Institution | University of Fukui |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2013
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| Keywords | 白血病 / 化学療法 / 機能薬理 / 耐性克服 / テーラーメイド / ヌクレオシドアナログ |
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| Research Abstract |
To establish pharmacologicaly-directed tailor-made chemotherapy for leukemia, the mechanisms of action and resistance of clofarabine were investigated using two newly developed clofarabine-resistant leukemic cell lines.
The resistant cell lines exhibited reduced clofarabine triphosphate production due to decreased mRNA levels of 3 cell membrane transporters and low protein levels of 2 kinases. The cell lines also showed increased Bcl-2 protein levels, suggestive of antiapoptosis. A cytarabine-resisntant leukemic cell line that had been previously develped showed reduction in only one transporter and one kinase, and 1/10 reduced cytarabine triphosphate. This cell line still possessed the sensitivity to clofarabine, which was atttibutable to the capacity to produce clofarabine triphosphate.
Thus, pharmacologically-directed tailor-made chemotherapy will be established using surrogate markers (intracellular triphosphate production and Bcl-2 exression) to overcome resistance of leukemia.
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[Journal Article] Role of hematopoietic stem cell transplantation as salvage treatment for acute promyelocytic leukemia initially treated with all-trans-retinoic acid and chemotherapy2013
Author(s)
Fujita H, Asou N, Iwanaga M, Hyo R, Nomura S, Kiyoi H, Okada M, Tsuzuki M, Matsuda M, Yamauchi T, 他
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Journal Title
Cancer Sci
Volume: 104
Pages: 1339
Peer Reviewed
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