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酪氨酸激酶抑制剂在嗜酸性粒细胞肿瘤和系统性肥大细胞增多症治疗中的应用

Tyrosine Kinase Inhibitors in the Treatment of Eosinophilic Neoplasms and Systemic Mastocytosis.

作者信息

Gotlib Jason

机构信息

Division of Hematology, Stanford Cancer Institute/Stanford University School of Medicine, 875 Blake Wilbur Drive, Room 2324, Stanford, CA 94305-5821, USA.

出版信息

Hematol Oncol Clin North Am. 2017 Aug;31(4):643-661. doi: 10.1016/j.hoc.2017.04.009.

Abstract

The World Health Organization's semimolecular classification of eosinophilias emphasizes neoplasms driven by fusion tyrosine kinases. More than 80% of patients with systemic mastocytosis carry the KIT D816V mutation, the primary driver of disease pathogenesis. Genetic annotation of these diseases is critical and affords opportunities for targeted therapy. This article discusses our understanding of the mutated tyrosine kinome of eosinophilic neoplasms and systemic mast cell disease, and the successes and limitations of available therapies. Use of tyrosine kinase inhibitors as a bridge to hematopoietic stem cell transplantation, and development of more selective and potent tyrosine kinase inhibitors is also highlighted.

摘要

世界卫生组织对嗜酸性粒细胞增多症的半分子分类强调由融合酪氨酸激酶驱动的肿瘤。超过80%的系统性肥大细胞增多症患者携带KIT D816V突变,这是疾病发病机制的主要驱动因素。这些疾病的基因注释至关重要,并为靶向治疗提供了机会。本文讨论了我们对嗜酸性粒细胞肿瘤和系统性肥大细胞疾病突变酪氨酸激酶组的理解,以及现有疗法的成功与局限性。还强调了使用酪氨酸激酶抑制剂作为造血干细胞移植的桥梁,以及开发更具选择性和强效的酪氨酸激酶抑制剂。

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