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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Downstream targets of FLT3-ITD in Ara-C resistance of leukemic cells

演題番号 : OS-1-96

Anar Damdinsuren:1、松下 弘道 (Hiromichi Matsushita):1、Masatoshi Ito:2、Masatoshi Ito:2、Hideo Tsukamoto:2、Masayuki Tanaka:2、松澤 秀之 (Hideyuki Matsuzawa):2、Satomi Asai:1、安藤 潔 (Kiyoshi Ando):3、宮地 隼人 (Hayato Miyachi):1

1:Department of Laboratory Medicine, Tokai University, School of Medicine, Japan、2:Education and Research Support Center, Tokai University, School of Medicine、3:Department of Hematology and Oncology, Tokai University, School of Medicine

 

One of the most frequent mutations associated with AML is an internal tandem duplication (ITD) in the juxtamembrane region of the receptor tyrosine kinase FLT3. It is found in 25-35% of AML patients and is associated with poor prognosis. FLT3-ITD causes constant activation of the specific signaling pathways, which lead to enhancement of proliferation in vitro as well as in vivo. But its relationship to drug resistance is still largely unknown.Previously we have reported a specific resistance of the leukemic cells with FLT3-ITD to cytosine arabinoside (Ara-C), an essential agent for the treatment of AML, accompanied by downregulation of equilibrative nucleoside transporter 1 and upregulation of hypoxia inducible factor 1 alpha subunit (Biochem Biophys Res Commun 390:1001, 2009).To understand comprehensive biological processes responsible for the drug resistance to Ara-C, we generated retroviral vectors with two types of FLT3-ITD. Both conferred Ara-C resistance in K562 human leukemic cell line without cross-resistance to other agents, such as idarubicine, etoposide, vincristine and methotrexate. To clarify in detail the molecular mechanism behind this specificity, we performed gene expression profiling of the FLT3-ITD expressing K562 cells by cDNA microarray analysis. Among 41,000 genes, 311 and 18 were up- and down-regulated respectively. Of these, some genes have been previously reported to participate in drug resistance and/or survival of leukemic cells. We are now investigating to evaluate whether these genes contributes to FLT3-ITD mediated Ara-C resistance.

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