Divisions of Hematology and.
Medical Oncology, Stanford University School of Medicine/Stanford Cancer Institute, Stanford, CA.
Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):127-136. doi: 10.1182/asheducation-2018.1.127.
Mastocytosis is a rare disease characterized by KIT-driven expansion and accumulation of neoplastic mast cells in various tissues. Although mediator symptoms related to mast cell activation can impose a symptom burden in cutaneous disease and across the spectrum of systemic mastocytosis subtypes, the presence of an associated hematologic neoplasm and/or organ damage denotes advanced disease and the potential for increased morbidity and mortality. In addition to the revised 2016 World Health Organization classification of mastocytosis, a new diagnostic and treatment toolkit, tethered to enhanced molecular characterization and monitoring, is poised to transform the management of patients with advanced systemic mastocytosis (advSM). Although the efficacy of midostaurin and novel selective KIT D816V inhibitors, such as avapritinib (BLU-285), have validated KIT as a therapeutic target, the clinical and biologic heterogeneity of advSM requires that we reimagine the blueprint for tackling these diseases and use tools that move beyond KIT-centric approaches.
肥大细胞增多症是一种罕见疾病，其特征是 KIT 驱动的肿瘤性肥大细胞在各种组织中的扩增和积累。尽管与肥大细胞激活相关的介质症状会给皮肤疾病和全身性肥大细胞增多症亚型的各个方面带来症状负担，但伴发的血液学肿瘤和/或器官损伤表明疾病进展，并可能增加发病率和死亡率。除了修订后的 2016 年世界卫生组织肥大细胞增多症分类外，一种新的诊断和治疗工具包，与增强的分子特征和监测相关联，有望改变晚期系统性肥大细胞增多症（advSM）患者的管理。虽然 midostaurin 和新型选择性 KIT D816V 抑制剂（如 avapritinib [BLU-285]）的疗效已经验证了 KIT 作为治疗靶点的作用，但 advSM 的临床和生物学异质性要求我们重新构想解决这些疾病的蓝图，并使用超越 KIT 为中心的方法的工具。
