演題詳細

一般口演 / Oral Session

【E】一般口演 19 (Oral Session 19) :AML:Mechanism of Therapeutic Agent

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日程
2013年10月11日(金)
時間
14:25 - 15:25
会場
第4会場 / Room No.4 (さっぽろ芸文館 3F 黎明)
座長・司会
小林 正夫 (Masao Kobayashi):1
1:Department of Pediatrics, Graduate School of Biomedical & Health Sciences, Hiroshima University, Japan
 
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Inhibitory effects of FL on proliferation and FLT3 inhibitors in Wt- and ITD-FLT3-coexpressing cells

演題番号 : OS-1-97

陳 昉里 (Fangli Chen):1、中谷 俊幸 (Toshiyuki Nakatani):1、木原 里香 (Rika Kihara):1、直江 知樹 (Tomoki Naoe):1、清井 仁 (Hitoshi Kiyoi):1

1:Department of Hematology/Oncology, Nagoya University Graduate School of Medicine, Japan

 

Purpose:FLT3-ITD mutations are frequently identified in acute myeloid leukemia (AML) patients, and associated with poor prognosis. Several FLT3 inhibitors are undergoing investigation. Their inhibitory effects were mainly evaluated using the sole mutant FLT3-expressing cells in pre-clinical studies, while most AML cells harboring FLT3 mutation co-express wild-type (Wt) FLT3, suggesting that FL-dependent Wt-FLT3 signal might cause the lower clinical efficacy than expected. Here we analyzed how FL-dependent Wt-FLT3 signal affects the inhibitory effect of FLT3 inhibitors and proliferation on Wt- and ITD (Wt/ITD)-FLT3-coexpressing cells.Method: We established several Wt/ITD-FLT3-coexpressing 32D cells, and growth inhibitory effects of 6 inhibitors were evaluated with and without FL stimulation. Furthermore, we investigated how FL affects the proliferation and viability of Wt/ITD-FLT3-coexpressing cells both in vitro and in vivo.Result: The FL-stimulation reduced growth inhibitory effects by FLT3 inhibitors on Wt/ITD-FLT3-coexpressing 32D cells, while those reducing effects were little on the sole extracellular domain lacked ITD-FLT3 expressing cells. Of note is that FL-stimulation reduces proliferation and viability of Wt/ITD-FLT3-coexpressing cells. Furthermore, all syngeneic C3H mice inoculated with sole ITD-FLT3-expressing 32D cells died by leukemia, but not with Wt/ITD-FLT3-coexpressing cells.Conclusion: These results suggested that the FL-stimulation might reduce the cell proliferation and inhibitory effects of FLT3 inhibitors through the interaction with Wt-FLT3.

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