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首页> 外文期刊>Nature >BCL6 enables Ph~+ acute lymphoblastic leukaemia cells to survive BCR-ABL1 kinase inhibition
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BCL6 enables Ph~+ acute lymphoblastic leukaemia cells to survive BCR-ABL1 kinase inhibition

机译：BCL6使Ph〜+急性淋巴细胞白血病细胞能够抑制BCR-ABL1激酶

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摘要

Tyrosine kinase inhibitors (TKIs) are widely used to treat patients with leukaemia driven by BCR-ABL1 (ref. 1) and other oncogenic tyrosine kinases. Recent efforts have focused on developing more potent TKIs that also inhibit mutant tyrosine kinases. However, even effective TKIs typically fail to eradicate leukaemia-initiating cells (LICs), which often cause recurrence of leukaemia after initially successful treatment. Here we report the discovery of a novel mechanism of drug resistance, which is based on protective feedback signalling of leukaemia cells in response to treatment with TKI. We identify BCL6 as a central component of this drug-resistance pathway and demonstrate that targeted inhibition of BCL6 leads to eradication of drug-resistant and leukaemia-initiating subclones.
机译：酪氨酸激酶抑制剂（TKIs）被广泛用于治疗由BCR-ABL1（参考文献1）和其他致癌酪氨酸激酶驱动的白血病患者。最近的努力集中在开发更有效的TKIs上，这些TKIs也抑制突变酪氨酸激酶。但是，即使有效的TKI通常也无法根除白血病起始细胞（LICs），这通常会在最初获得成功的治疗后导致白血病复发。在这里，我们报告了一种新型耐药机制的发现，该机制基于对TKI治疗产生反应的白血病细胞的保护性反馈信号。我们确定BCL6为这种耐药途径的主要组成部分，并证明BCL6的靶向抑制作用导致根除耐药性和白血病起始亚克隆。

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  • 来源
    《Nature 》 |2011年第7347期| p.384-388| 共5页
  • 作者

    Cihangir Duy; Christian Hurtz; Seyedmehdi Shojaee; Leandro Cerchietti; Huimin Geng; Srividya Swaminathan; Lars Klemm; Soo-mi Kweon; Rahul Nahar; Melanie Braig; Eugene Park; Yong-mi Kim; Wolf-Karsten Hofmann; Sebastian Herzog; Hassan Jumaa; H. Phillip Koeffler; J. Jessica Yu; Nora Heisterkamp; Thomas G. Graeber; Hong Wu; B. Hilda Ye; Ari Melnick; Markus Mueschen;

  • 作者单位

    Department of Laboratory Medicine, University of California San Francisco, San Francisco, California 94143, USA,Children's Hospital Los Angeles, Department of Pediatrics, University of Southern California, Los Angeles, California 90027, USA;

    Department of Laboratory Medicine, University of California San Francisco, San Francisco, California 94143, USA,Faculty of Biology, BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-Universitat Freiburg and Max-Planck-lnstitute for Immunobiology, Freiburg, Germany;

    Department of Laboratory Medicine, University of California San Francisco, San Francisco, California 94143, USA;

    Departments of Medicine and Pharmacology, Weill Cornell Medical College, New York, New York 10065, USA;

    Departments of Medicine and Pharmacology, Weill Cornell Medical College, New York, New York 10065, USA;

    Department of Laboratory Medicine, University of California San Francisco, San Francisco, California 94143, USA;

    Department of Laboratory Medicine, University of California San Francisco, San Francisco, California 94143, USA;

    Children's Hospital Los Angeles, Department of Pediatrics, University of Southern California, Los Angeles, California 90027, USA;

    Department of Laboratory Medicine, University of California San Francisco, San Francisco, California 94143, USA,Children's Hospital Los Angeles, Department of Pediatrics, University of Southern California, Los Angeles, California 90027, USA;

    Department of Hematology and Oncology,Universitatsklinikum Hamburg-Eppendorf, Hamburg, Germany;

    Children's Hospital Los Angeles, Department of Pediatrics, University of Southern California, Los Angeles, California 90027, USA;

    Children's Hospital Los Angeles, Department of Pediatrics, University of Southern California, Los Angeles, California 90027, USA;

    Department of Hematology and Oncology, Universitat Heidelberg, Klinikum Mannheim, Mannheim, Germany;

    Faculty of Biology, BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-Universitat Freiburg and Max-Planck-lnstitute for Immunobiology, Freiburg, Germany;

    Faculty of Biology, BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-Universitat Freiburg and Max-Planck-lnstitute for Immunobiology, Freiburg, Germany;

    Division of Hematology and Oncology, Cedars Sinai Medical Center, Los Angeles,California 90095, USA;

    Department of Cell Biology,Albert Einstein College of Medicine, Bronx, New York 10461, USA;

    Children's Hospital Los Angeles, Department of Pediatrics, University of Southern California, Los Angeles, California 90027, USA;

    Department of Molecular Pharmacology, University of California Los Angeles, Los Angeles, California 90095,USA;

    Department of Molecular Pharmacology, University of California Los Angeles, Los Angeles, California 90095,USA;

    Department of Cell Biology,Albert Einstein College of Medicine, Bronx, New York 10461, USA;

    Departments of Medicine and Pharmacology, Weill Cornell Medical College, New York, New York 10065, USA;

    Department of Laboratory Medicine, University of California San Francisco, San Francisco, California 94143, USA,Children's Hospital Los Angeles, Department of Pediatrics, University of Southern California, Los Angeles, California 90027, USA;

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