| Budget Amount *help |
¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Outline of Final Research Achievements |
In order to elucidate the molecular pathogenesis and diagnostic marker of refractory leukemia, molecular mechanisms of cytosine arabinoside resistant leukemia cell K562 cells which possess prognostically poor biomarkers, an internal tandem duplication (ITD) of the receptor tyrosine kinase FLT3. Microarray analysis of the FLT3-ITD-transduced K562 leukemia cell line revealed 311 up-regulated genes. Among them we found transcriptional induction by FLT3-ITD of the runt-domain-containing transcriptional factor RUNX3. FLT3-ITD increased RUNX3 promoter activity in a reporter assay, which was hampered by the inhibitors. shRNA knockdown of RUNX3 in the cells resulted in an increased sensitivity to Ara-C. Exogenous overexpression of RUNX3 per se in K562 cells resulted in enhanced Ara-C resistance. These results suggest that RUNX3 could be a prerequisite for Ara-C resistance via FLT3-ITD signaling, and thus an important candidate of biomarker of the refractory AML.
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