| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Outline of Final Research Achievements |
CCRF-CEM cells were incubated with nelarabine by the limiting dilution method and two nelarabine-resistant clones were established. The resistant clones had higher IC50 (55 and 78 times higher) than the parent clone in the MTT assay. The expressions of ENT1, DCK, and DGuoK mRNAs associated with nelarabine metabolism were significantly down-regulated in resistant clones; demethylation of the promoter region of DCK was not involved. The resistant clones showed increased expression of p-Akt, suggesting increased expression of the PI3K/AKT pathway. In addition, p-ERK hyperactivation was observed after 72 hours of nelarabine treatment. Overactivation of the MEK/ERK pathway specific to the nelarabine metabolic pathway was thought to be the cause of resistance.
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