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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Role of SF3B1 on hematopoiesis

演題番号 : OS-1-170

松縄 学 (Manabu Matsunawa):1、山本 玲 (Ryo Yamamoto):2、真田 昌 (Masashi Sanada):1,4、吉田 健一 (Kenichi Yoshida):1、永田 安伸 (Yasunobu Nagata):1、昆 彩奈 (Ayana Kon):1、吉里 哲一 (Tetsuichi Yoshizato):1、大津 真 (Makoto Otsu):2、磯野 協一 (Kyoichi Isono):3、古関 明彦 (Haruhiko Koseki):3、中内 啓光 (Hiromitsu Nakauchi):2、小川 誠司 (Seishi Ogawa):1,4

1:Cancer Genomics Project, Graduate School of Medicine, Tokyo Univ、2:Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, The University of Tokyo、3:Developmental Genetics Group, RIKEN Research Center for Allergy and Immunology、4:Pathology and Tumor Biology, Graduate School of Medicine, Kyoto Univ

 

Recently, we and other groups reported frequent pathway mutations involving multiple components of the RNA splicing machinery in myelodysplastic syndromes (MDS). In particular, SF3B1 mutations were strongly associated with MDS subtypes characterized by increased ring sideroblasts (RS), suggesting the critical role of SF3B1 mutations in these MDS subtypes. SF3B1 encodes one of the core components of the U2 snRNP, which is involved in pre-mRNA splicing. In an animal experiment, Sf3b1 null mice were shown to be embryonic lethal, whereas Sf3b1 +/- mice exhibited various skeletal alterations that were attributed to deregulation of Hox gene expression. However, no detailed analysis of hematopoietic system in Sf3b1 +/- mice has been reported. So, to clarify the role of SF3B1 in hematopoiesis, we investigated the hematological phenotype of Sf3b1 +/- mice. There was no significant difference in peripheral blood counts, bone marrow (BM) lineage distribution, and BM total cellularity between Sf3b1 +/+ and +/- mice. No particular morphologic changes including bone marrow dysplasia and increased RS were observed. In contrast, quantitative analysis of BM cells from Sf3b1 +/- mice revealed a reduction of the number of hematopoietic stem cells. In accordance with this, Sf3b1 +/- mice showed lower colony forming capacity in vitro, and Sf3b1 +/- mice had impaired competitive reconstitution capacity in vivo. These data demonstrated that Sf3b1 plays a role in regulation of normal hematopoiesis.

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