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J-GLOBAL ID：201802261922101319   整理番号：18A0158518

TET2損失およびNRAS変異による協同的後成的リモデリング骨髄形質転換およびMEK阻害剤感受性を促進する【Powered by NICT】

Cooperative Epigenetic Remodeling by TET2 Loss and NRAS Mutation Drives Myeloid Transformation and MEK Inhibitor Sensitivity

著者 (35件)： Kunimoto Hiroyoshi (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Kunimoto Hiroyoshi (Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Kunimoto Hiroyoshi (Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Meydan Cem (Institute for Computational Biomedicine and Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY 10065, USA) ,  Nazir Abbas (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Nazir Abbas (Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Nazir Abbas (Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Whitfield Justin (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Whitfield Justin (Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Whitfield Justin (Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Shank Kaitlyn (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Shank Kaitlyn (Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Shank Kaitlyn (Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Rapaport Franck (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Rapaport Franck (Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Maher Rebecca (University of Connecticut School of Medicine, Farmington, CT 06032, USA) ,  Pronier Elodie (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Pronier Elodie (Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Pronier Elodie (Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Meyer Sara C. (Division of Hematology, University Hospital Basel, 4031 Basel, Switzerland) ,  Meyer Sara C. (Department of Biomedicine, University Hospital Basel, 4031 Basel, Switzerland) ,  Garrett-Bakelman Francine E. (Department of Medicine, Division of Hematology-Oncology, Weill Cornell Medical College, New York, NY 10065, USA) ,  Garrett-Bakelman Francine E. (Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA) ,  Garrett-Bakelman Francine E. (Department of Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, USA) ,  Tallman Martin (Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Melnick Ari (Department of Medicine, Division of Hematology-Oncology, Weill Cornell Medical College, New York, NY 10065, USA) ,  Melnick Ari (Department of Pharmacology, Weill Cornell Medical College, New York, NY 10065, USA) ,  Levine Ross L. (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Levine Ross L. (Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Levine Ross L. (Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Levine Ross L. (Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Shih Alan H. (Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Shih Alan H. (Center for Epigenetics Research, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Shih Alan H. (Center for Hematologic Malignancies, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA) ,  Shih Alan H. (Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA)
資料名： Cancer Cell  (Cancer Cell)
巻： 33  号： 1  ページ： 44-59.e8  発行年： 2018年 
JST資料番号： W1844A  ISSN： 1535-6108  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： オランダ (NLD)  言語： 英語 (EN)

抄録/ポイント： 後成的修飾因子とシグナル伝達因子の変異は骨髄性悪性腫瘍における共存の場合,TET2およびNRAS突然変異を含む。造血細胞における同時Tet2損失とNras~G12D発現は骨髄形質転換を誘導し,完全な浸透,致死慢性骨髄単球性白血病(CMML)であり,連続的に移植可能であった。Tet2損失とNras突然変異は協調的にマイトジェン活性化蛋白質キナーゼ(MAPK)活性化の負の調節因子,Spry2を含むを低下し,それにより後成的サイレンシングによるMAPKシグナル伝達の相乗的活性化を引き起こした。Tet2/Nras二重変異体白血病マウスモデルおよび患者試料の両方においてMAPKキナーゼ(MEK)阻害への優先的な感度を示した。これらのデータは,後成的シグナル伝達変異は骨髄形質転換において協調するかについての洞察を提供し,これらの高リスク遺伝的病変を有するCMML患者における作用機序ベース治療のための理論的根拠を提供する。Copyright 2018 Elsevier B.V., Amsterdam. All rights reserved. Translated from English into Japanese by JST.【Powered by NICT】

シソーラス用語： MAPキナーゼ ,  白血病 ,  *感受性 ,  突然変異 ,  *骨髄 ,  患者 ,  遺伝子サイレンシング ,  *変異
準シソーラス用語： キナーゼ ,  マウスモデル ,  調節因子 ,  造血細胞 ,  悪性腫瘍 ,  *リモデリング ,  *TET2 , 【Automatic Indexing@JST】

著者キーワード (3件)： 白血病生物学 ,  癌エピジェネティクス ,  標的治療

分類 (2件)： 細胞生理一般  (EF02010S) ,  遺伝子発現  (EC02040Q)

タイトルに関連する用語 (11件)： TET2 ,  損失 ,  NRAS ,  変異 ,  協同 ,  リモデリング ,  骨髄 ,  形質転換 ,  MEK阻害剤 ,  感受性 ,  促進