演題詳細

一般口演 / Oral Session

一般口演 34 (Oral Session 34) :MDS/MPN:基礎 2

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日程
2013年10月11日(金)
時間
15:25 - 16:25
会場
第14会場 / Room No.14 (札幌市教育文化会館 3F 研修室305)
座長・司会
原田 浩徳 (Hironori Harada):1
1:順天堂大学 血液内科
 
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Methylation of stromal HHIP gene could be associated with proliferation of myeloid neoplastic cells

演題番号 : OS-1-173

堀口 拓人 (Hiroto Horiguchi):1、小船 雅義 (Masayoshi Kobune):1、菊地 尚平 (Shohei Kikuchi):1、井山 諭 (Satoshi Iyama):1、高田 弘一 (Kouichi Takada):1、小野 薫 (Kaoru Ono):1、神原 悠輔 (Yusuke Kamihara):1、佐藤 勉 (Tsutomu Sato):1、林 毅 (Tsuyoshi Hayashi):1、宮西 浩嗣 (Koji Miyanishi):1、佐藤 康史 (Yasushi Sato):1、瀧本 理修 (Rishu Takimoto):1、加藤 淳二 (Junji Kato):1

1:Sapporo Univ. School of Med., Medical Oncology and Hematology

 

Aberrant reactivation of Hedgehog (Hh) signaling has been described in a wide variety of human cancers including cancer-initiating cells. However, involvement of the Hh signaling system in the bone marrow (BM) microenvironment during the development of myeloid neoplasm is controversial. In this study we assessed the expression of Hh-related proteins in normal human CD34+ cells, CD34+ leukemic/dysplastic cells and BM stromal cells. Both Indian hedgehog (Ihh) and its signal transducer, Smoothed (SMO), were expressed in normal CD34+ cells, CD34+ acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) derived cells, suggesting that Ihh could be affected in an autocrine manner. Remarkably, expression of the endogenous Hh signaling inhibitor, human hedgehog-interacting protein (HHIP), in AML/MDS-associated stromal cells was significantly reduced as compared with that in healthy donor-derived stromal cells. Moreover, HHIP expression level in BM stromal cells highly correlated with their tumor-supporting activity of CD34+/SMO+ leukemic cells. Demethylating agent 5-aza-dC rescued HHIP expression via demethylation of HHIP gene and reduced the leukemia-supporting activity of AML/MDS-derived stromal cells. This effect of 5-aza-dC was negated by HHIP shRNA transfer into stromal cells. These results indicate that suppression of stromal HHIP expression could be involved in the progression of AML/MDS and 5-aza-dC may improve the protective function of BM stromal cells for AML/MDS.

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