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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Chromosomal instability due to downregulation of Miki, a del(7q)-responsible gene product

演題番号 : OS-1-172

尾崎 佑子 (Yuko Ozaki):1、松井 啓隆 (Hirotaka Matsui):1、長町 安希子 (Akiko Nagamachi):1、安藝 大輔 (Daisuke Aki):2、稲葉 俊哉 (Toshiya Inaba):1

1:Research Inst. for Radiation Biology and Medicine, Hiroshima Univ, Japan、2:La Jolla Institute for Allergy and Immunology

 

We isolated a gene encoding a centrosome protein, Miki (mitotic kinetics regulator), from 7q21.3 sub-band as a candidate responsible gene for AML and MDS carrying monosomy 7 and/or del(7q) (Mol. Cell 2012). Miki-downregulation in K562 erythroleukemia cells by short hairpin (sh)-RNA inhibited progression of prometaphase, resulting in marked chromosomes scattering, lagging chromosomes, pseudo-metaphase and premature chromosome decondensation (PCDC: chromosomes decondense before segregation that results in the formation of small nuclei). These mitotic impairment induced abnormal nuclear morphology such as bi-, tri- or multiple-nuclei with or without small nuclei and resulted in a wide variation of chromosome number. Cell lines harboring monosomy 7 such as F-36P and MDS-L expressed Miki at barely detectable levels. Giemsa staining of these cells showed abnormal mitosis and nuclear abnormalities observed in K562 cells expressing Miki at low levels that can be reversed by retrovirus-mediated Miki expression. In addition, multiple small nuclei as a result of PCDC were observed in the bone marrow pictures of MDS and AML patients associated with monosomy 7 at high frequency. These results suggested that chromosome instability due to Miki-downregulation causes aneuploidy that subsequently induces progression of MDS and AML.

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