2014 Fiscal Year Final Research Report
Establishment of predictive marker for epigenetic drugs in hematological malignancies
| Project/Area Number |
23590687
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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 |
Laboratory medicine
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| Research Institution | Kitasato University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
SATOH Takashi 北里大学, 医療衛生学部, 講師 (90407114)
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| Project Period (FY) |
2011-04-28 – 2015-03-31
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| Keywords | バイオマーカー / 分化 / PU.1 / メタロチオネイン / 白血病 |
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| Outline of Final Research Achievements |
First, we examined the effect of DNA methylation inhibitor on various PU.1 transgenic leukemia cell lines. As a result, we found a positive correlations for PU.1 expression and DNA methylation inhibitor effect, which induced differentiation and finally elimination of leukemia cells. Next, we assessed whether this effect is correlated with metallothionein (MT) expression, which we recently found an novel suppressive target gene of PU.1. To this aim, we generated MT over-expressed acute promyelocytic leukemia NB4 cell line (NB4MTOEcells) and examined the effect of all-trans retinoic acid (ATRA), which is a potent differentiation inducer for NB4 cells. We revealed that the effect of ATRA is inhibited in NB4MTOE cells. This is quite consistent with our prediction, because PU.1 is a suppressive regulator of MT. Collectively, these results suggest that expressions of PU.1 and MT may serve as useful biomarkers to predict the efficacy of epigenetic drugs which have differentiation effects.
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| Free Research Field |
病態検査学
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