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表达ETV6::FRK的白血病细胞在体内对达沙替尼敏感。

Leukaemic cells expressing ETV6::FRK are sensitive to dasatinib in vivo.

作者信息

Mayumi Azusa, Imamura Toshihiko, Yoshida Hideki, Osone Shinya, Yasuda Takahiko, Iehara Tomoko

机构信息

Department of Paediatrics Kyoto Prefectural University of Medicine Kyoto Japan.

Clinical Research Center Nagoya Medical Centre National Hospital Organization Nagoya Japan.

出版信息

EJHaem. 2023 May 2;4(3):751-755. doi: 10.1002/jha2.701. eCollection 2023 Aug.

Abstract

ETV6::Fyn-related kinase (FRK), which is a Src family tyrosine-kinase-related fusion gene and firstly identified in our patient with paediatric high risk B cell precursor acute lymphoblastic leukaemia (B-ALL), has no evidence of efficacy of tyrosine kinase inhibitor in vivo. We performed functional analysis of ETV6::FRK to establish molecular targeting therapy and determined that dasatinib could abrogate proliferation activity of ETV6::FRK through the repression of FRK-STAT3/STAT5 pathway in vitro and significantly extended the survival time of the xenografted mice in vivo ( < 0.01). Our data support the potential of dasatinib as a therapeutic option for patients with B-ALL harboring FRK rearrangements.

摘要

ETV6::Fyn相关激酶(FRK)是一种Src家族酪氨酸激酶相关融合基因,首次在我们的小儿高危B细胞前体急性淋巴细胞白血病(B-ALL)患者中发现,尚无酪氨酸激酶抑制剂在体内有效的证据。我们对ETV6::FRK进行功能分析以建立分子靶向治疗,并确定达沙替尼可通过在体外抑制FRK-STAT3/STAT5途径消除ETV6::FRK的增殖活性,并在体内显著延长异种移植小鼠的存活时间(<0.01)。我们的数据支持达沙替尼作为携带FRK重排的B-ALL患者治疗选择的潜力。

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