演題詳細

一般口演 / Oral Session

一般口演 22 (Oral Session 22) :造血幹細胞移植:基礎

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日程
2013年10月11日(金)
時間
15:25 - 16:25
会場
第5会場 / Room No.5 (さっぽろ芸文館 3F 清流)
座長・司会
村田 誠 (Makoto Murata):1
1:名古屋大学医学部附属病院 血液内科
 
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Sustained anti-leukemic activity of TRAIL against Ph+ leukemia cells in hypoxic environment

演題番号 : OS-1-113

杣津 晋平 (Shinpei Somazu):1、犬飼 岳史 (Takeshi Inukai):1、黒田 格 (Itaru Kuroda):1、八木田 秀雄 (Hideo Yagita):2、合井 久美子 (Kumiko Goi):1、大城 浩子 (Hiroko Ohshiro):1、渡邊 敦 (Atsushi Watanabe):1、宇野 佳奈子 (Kanako Uno):1、黄 媚賢 (Meixian Huang):1、加賀美 美恵子 (Mieko Kagami):1、小鹿 学 (Satoru Kojika):1、佐藤 広樹 (Hiroki Sato):1、古市 嘉行 (Yoshiyuki Furuichi):1、高橋 和也 (Kazuya Takahashi):1、廣瀬 衣子 (Kinuko Hirose):1、杉田 完爾 (Kanji Sugita):1

1:Pediatrics Yamanashi Univ., Japan、2:Immunology Juntendo Univ., Japan

 

GVL effect after allogeneic stem cell transplantation is mediated by TRAIL, one of cytotoxic factors expressing on cytotoxic T cell and NK cell, at least in part. We previously reported that Ph+ leukemias are frequently sensitive to anti-leukemia activity of TRAIL (Blood,2003) and that BCR-ABL itself plays an essential role in death receptor expression for TRAIL (Oncogene 2013). In clinical practice, it is assumed that GVL effect could eradicate residual Ph+ leukemic stem cells that survive after conventional chemotherapy. Since leukemic stem cells reside in hypoxic environment of bone marrow, we analyzed sensitivities of Ph+ leukemia cell lines to chemotherapeutic agents and recombinant human soluble (rhs) TRAIL in both normoxic and hypoxic conditions in vitro. Of note, 4 TRAIL-sensitive Ph+ leukemia cell lines (KOPM30, Nalm1, YAMN73, and KOPN66bi) were significantly resistant to VP-16, DNR, and Ara-C in 1% O2 condition than in 21% O2 condition. In contrast, these 4 Ph+ leukemia cell lines were sensitive to rhsTRAIL in both conditions. Consistently, cell surface and gene expression levels of death receptors for TRAIL in 4 Ph+ leukemia cell lines were almost unchanged in 1% and 5% O2 conditions in comparison with 21% O2 condition. These observations indicate that in hypoxic bone marrow environment anti-leukemic activity of TRAIL is not impaired whereas sensitivity to conventional chemotherapeutic agents are impaired, suggesting that TRAIL could be implicated in eradication of residual Ph+ leukemic stem cells by GVL effect.

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