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在组织细胞肿瘤中 CSF1R 和其他受体酪氨酸激酶的激活突变。

Activating mutations in CSF1R and additional receptor tyrosine kinases in histiocytic neoplasms.

机构信息

Human Oncology and Pathogenesis Program, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

出版信息

Nat Med. 2019 Dec;25(12):1839-1842. doi: 10.1038/s41591-019-0653-6. Epub 2019 Nov 25.

DOI:10.1038/s41591-019-0653-6
PMID:31768065
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6898787/
Abstract

Histiocytoses are clonal hematopoietic disorders frequently driven by mutations mapping to the BRAF and MEK1 and MEK2 kinases. Currently, however, the developmental origins of histiocytoses in patients are not well understood, and clinically meaningful therapeutic targets outside of BRAF and MEK are undefined. In this study, we uncovered activating mutations in CSF1R and rearrangements in RET and ALK that conferred dramatic responses to selective inhibition of RET (selpercatinib) and crizotinib, respectively, in patients with histiocytosis.

摘要

组织细胞增多症是一种克隆性造血系统疾病，常由 BRAF 和 MEK1 及 MEK2 激酶的突变驱动。然而，目前患者中组织细胞增多症的发展起源尚不清楚，除 BRAF 和 MEK 之外，临床上有意义的治疗靶点尚未确定。在这项研究中，我们发现 CSF1R 的激活突变以及 RET 和 ALK 的重排分别赋予了患者对 RET 选择性抑制（塞尔帕替尼）和克唑替尼的显著反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d62d/6898787/d23c3f123ff8/nihms-1541330-f0002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d62d/6898787/e32874fe11d5/nihms-1541330-f0008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d62d/6898787/641b33635b04/nihms-1541330-f0009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d62d/6898787/97fb035bf328/nihms-1541330-f0010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d62d/6898787/c2035ed5c4fc/nihms-1541330-f0011.jpg
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