| Project/Area Number |
25860792
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Hematology
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| Research Institution | Kyoto Prefectural University of Medicine |
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Principal Investigator |
SUGITANI Mio 京都府立医科大学, 医学部附属病院, 研究員 (60648749)
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| Co-Investigator(Kenkyū-buntansha) |
TANIWAKI Masafumi 京都府立医科大学, 医学部附属病院, 教授 (80163640)
KURODA Junya 京都府立医科大学, 医学部附属病院, 講師 (70433258)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 慢性骨髄性白血病 / Galectin-3 / 骨髄腫瘍環境由来治療抵抗性 / オートクライン・パラクライン / 幹細胞能 |
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| Outline of Final Research Achievements |
Tyrosin kinase inhibitors(TKIs) for BCR-ABL have dramatically improved the outcome of chronic myelogenous leukemia(CML). However, the complete elimination of CML clones has been rarely achieved by TKIs due to a variety of protective mechanisms. One reason for TKI resistance is the bone marrow microenvironment(BMME)-mediated drug resistance. We found that BMME-induced galectin-3(Gal-3) in CML plays an important role in drug resistance in previous study. Furthermore, we in this study disclosed the results as follows. ①The bovine SERPINA1-fetal bovine serum albumin complex was specifically suppressed in conditioned medium from Gal-3-overexpressing cells. Suppression of SERPINA1-albumin complex by Gal-3 overexpression led to paracrine growth promotion of CML cells. ②The combination of TKI and PP2A activator FTY720 could overcome Gal-3-mediated drug resistance to TKI. ③ALDH1 known as the marker of cancer stem cell and drug resistance was induced by Gal-3 overexpression in CML cells.
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