演題詳細

一般口演 / Oral Session

【E】一般口演 9 (Oral Session 9) :CML:Basic Research 1

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日程
2013年10月11日(金)
時間
09:30 - 10:30
会場
第7会場 / Room No.7 (ロイトン札幌 2F リージェント)
座長・司会
木村 晋也 (Shinya Kimura):1
1:Blood and Lung and Tumor Institute, Saga University, Japan
 
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Activity of imatinib and Jak kinase inhibitor: A potential treatment for Ph-positive leukemia cells

演題番号 : OS-1-44

岡部 聖一 (Seiichi Okabe):1、田内 哲三 (Tetsuzo Tauchi):1、片桐 誠一朗 (Seiichiro Katagiri):1、田中 裕子 (Yuko Tanaka):1、大屋敷 一馬 (Kazuma Ohyashiki):1

1:First Department of Internal Medicine, Tokyo Medical University, Japan

 

Imatinib is highly effective therapy against chronic myeloid leukemia (CML) patients. However, imatinib is not curative, because residual CML cells are present in bone marrow microenvironment. The hematopoietic cytokine receptor signaling is mediated by Janus kinases (Jaks) and signal transducers and activators of transcription (STATs). One of the Jak kinase inhibitor, TG101348 (SAR302503) is an orally available inhibitor of Jak2. Therefore, combination therapy using imatinib and a Jak inhibitor, TG101348 may help prevent stroma-associated drug resistance. We investigated the imatinib and TG101348 efficacy by using the Ph-positive cell lines, K562 and primary samples when leukemic cells were protected by the feeder cell (HS-5 and S9). The combination treatment with imatinib and TG101348 abrogated the protective effects of HS-5 conditioned media. Phosphorylation of BCR-ABL, Crk-L was significantly reduced and increased apoptosis. Combined treatment against CD34 positive primary samples with imatinib and TG101348 caused significantly more cytotoxicity. Mitogen-activated protein kinase (MAPK) was inhibited. Phosphorylation of BCR-ABL, Crk-L was significantly reduced and increased apoptosis. Moreover, combination of imatinib and TG101348 inhibited the colony growth. The cytokine production such as granulocyte macrophage colony-stimulating factor from HS-5 was also reduced. Data from this study suggested that administration of the imatinib and Jak inhibitor, TG101348 may be a powerful strategy against stroma-associated drug resistance of Ph-positive cells.

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