演題詳細

一般口演 / Oral Session

一般口演 3 (Oral Session 3) :AML:再発・難治性AML

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日程
2013年10月11日(金)
時間
09:30 - 10:30
会場
第4会場 / Room No.4 (さっぽろ芸文館 3F 黎明)
座長・司会
市川 幹 (Motoshi Ichikawa):1
1:湘南東部総合病院・クリニック 血液・腫瘍内科
 
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ITD-Flt3 accentuates cell migration by antagonizing the reduction of ROCK1 induced by SDF1

演題番号 : OS-1-15

大西 千恵 (Chie Onishi):1、平出 智裕 (Tomohiro Hirade):2、山口 清次 (Seiji Yamaguchi):2、福田 誠司 (Seiji Fukuda):2

1:Dept. of Hematology/Oncology, Shimane University School of Medicine, Izumo, Japan、2:Dept. of Pediatrics, Shimane University School of Medicine, Shimane, Japan

 

The minimal residual disease (MRD) of AML is believed to derive from leukemia cells that exist in osteoblastic niche where SDF1 is expressed. We reported that ITD-Flt3 mutations found in AML significantly enhance migration of hematopoietic cells to SDF1 (Blood 2005). These findings suggest that ITD-Flt3 facilitates retention and/or homing of AML cells to the marrow niche that expresses SDF1, which may contribute to the persistence of MRD. A recent report showed that Rho-Associated Kinase 1 (Rock1) enhances proliferation of ITD-Flt3+ cells (Cancer Cell 2012). Herein, we investigated if Rock1 is involved in the aberrant migration of ITD-Flt3+ cells to SDF1. The Rock1 expression was transiently up-regulated by SDF1, but significantly down-regulated after 4 hours in ITD-Flt3negative control Ba/F3 cells (N=3, P<0.01). However, the down-regulation of Rock1 that was induced by SDF1 in ITD-Flt3negative control cells was abrogated in the ITD-Flt3+ cells (N=3, P<0.05), coincident with enhancement in cell migration to SDF1. Rock1 antagonists or the shRNA for Rock1 abolished the enhanced migration of ITD-Flt3+ cells to SDF1 (N=3, P<0.05). These data demonstrate that ITD-Flt3 mutations increase cell migration to SDF1 by antagonizing the down-regulation of Rock1 expression that is normally induced by SDF1. Our findings implicate that targeting Rock1 may be therapeutically beneficial for MRD in the patients with ITD-Flt3+ AML by inhibiting the aberrant retention or chemotaxis of AML cells to marrow niche that expresses SDF1.

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