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巨核细胞在骨髓纤维化中的作用。

The Role of Megakaryocytes in Myelofibrosis.

机构信息

Division of Experimental Hematology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, MC341, Memphis, TN 38105, USA. Electronic address: https://twitter.com/melo_cardenas1.

Department of Biomedical and Neuromotor Sciences, University of Bologna, Via Irnerio, 48 - I 40126, Bologna, Italy.

出版信息

Hematol Oncol Clin North Am. 2021 Apr;35(2):191-203. doi: 10.1016/j.hoc.2020.11.004. Epub 2021 Jan 11.

DOI:10.1016/j.hoc.2020.11.004
PMID:33641863
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7921544/
Abstract

Megakaryocytes give rise to platelets, which have a wide variety of functions in coagulation, immune response, inflammation, and tissue repair. Dysregulation of megakaryocytes is a key feature of in the myeloproliferative neoplasms, especially myelofibrosis. Megakaryocytes are among the main drivers of myelofibrosis by promoting myeloproliferation and bone marrow fibrosis. In vivo targeting of megakaryocytes by genetic and pharmacologic approaches ameliorates the disease, underscoring the important role of megakaryocytes in myeloproliferative neoplasms. Here we review the current knowledge of the function of megakaryocytes in the JAK2, CALR, and MPL-mutant myeloproliferative neoplasms.

摘要

巨核细胞生成血小板,血小板在凝血、免疫反应、炎症和组织修复中具有多种功能。巨核细胞的失调是骨髓增生性肿瘤的一个关键特征,尤其是骨髓纤维化。巨核细胞通过促进骨髓增生和骨髓纤维化成为骨髓纤维化的主要驱动因素之一。通过遗传和药理学方法在体内靶向巨核细胞可改善疾病,这突显了巨核细胞在骨髓增生性肿瘤中的重要作用。在这里,我们回顾了巨核细胞在 JAK2、CALR 和 MPL 突变型骨髓增生性肿瘤中的功能的现有知识。

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The Role of Megakaryocytes in Myelofibrosis.巨核细胞在骨髓纤维化中的作用。
Hematol Oncol Clin North Am. 2021 Apr;35(2):191-203. doi: 10.1016/j.hoc.2020.11.004. Epub 2021 Jan 11.
2
CALR, JAK2, and MPL mutation profiles in patients with four different subtypes of myeloproliferative neoplasms: primary myelofibrosis, essential thrombocythemia, polycythemia vera, and myeloproliferative neoplasm, unclassifiable.四种不同亚型骨髓增殖性肿瘤患者(原发性骨髓纤维化、原发性血小板增多症、真性红细胞增多症和无法分类的骨髓增殖性肿瘤)的CALR、JAK2和MPL突变谱
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Somatic mutations of calreticulin in myeloproliferative neoplasms.髓系增殖性肿瘤中的钙网织蛋白体细胞突变。
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本文引用的文献

1
Increased CXCL4 expression in hematopoietic cells links inflammation and progression of bone marrow fibrosis in MPN.造血细胞中 CXCL4 表达增加将炎症与 MPN 骨髓纤维化的进展联系起来。
Blood. 2020 Oct 29;136(18):2051-2064. doi: 10.1182/blood.2019004095.
2
Thrombopoietin is required for full phenotype expression in a JAK2V617F transgenic mouse model of polycythemia vera.血小板生成素对于 JAK2V617F 转基因小鼠模型真性红细胞增多症的完全表型表达是必需的。
PLoS One. 2020 Jun 1;15(6):e0232801. doi: 10.1371/journal.pone.0232801. eCollection 2020.
3
Single-Cell Analyses Reveal Megakaryocyte-Biased Hematopoiesis in Myelofibrosis and Identify Mutant Clone-Specific Targets.单细胞分析揭示骨髓纤维化中巨核细胞偏向性造血并鉴定突变克隆特异性靶点。
Mol Cell. 2020 May 7;78(3):477-492.e8. doi: 10.1016/j.molcel.2020.04.008.
4
Single-cell analysis based dissection of clonality in myelofibrosis.单细胞分析解析骨髓纤维化中的克隆性。
Nat Commun. 2020 Jan 7;11(1):73. doi: 10.1038/s41467-019-13892-x.
5
Mutations associated with age-related clonal hematopoiesis in PMF patients with rapid progression to myelofibrosis.与 PMF 患者向骨髓纤维化快速进展相关的年龄相关克隆性造血突变。
Leukemia. 2020 May;34(5):1364-1372. doi: 10.1038/s41375-019-0668-5. Epub 2019 Nov 27.
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Progress in elucidation of molecular pathophysiology of myeloproliferative neoplasms and its application to therapeutic decisions.阐明骨髓增殖性肿瘤分子发病机制的进展及其在治疗决策中的应用。
Int J Hematol. 2020 Feb;111(2):182-191. doi: 10.1007/s12185-019-02778-9. Epub 2019 Nov 18.
7
Description of a knock-in mouse model of JAK2V617F MPN emerging from a minority of mutated hematopoietic stem cells.描述了一种 JAK2V617F MPN 的敲入小鼠模型,该模型源自少数突变造血干细胞。
Blood. 2019 Dec 26;134(26):2383-2387. doi: 10.1182/blood.2019001163.
8
Defective interaction of mutant calreticulin and SOCE in megakaryocytes from patients with myeloproliferative neoplasms.巨核细胞中突变钙网蛋白与 SOCE 的缺陷相互作用与骨髓增殖性肿瘤。
Blood. 2020 Jan 9;135(2):133-144. doi: 10.1182/blood.2019001103.
9
Mutant calreticulin in myeloproliferative neoplasms.骨髓增殖性肿瘤中的突变钙网织蛋白。
Blood. 2019 Dec 19;134(25):2242-2248. doi: 10.1182/blood.2019000622.
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Myelofibrosis in 2019: moving beyond JAK2 inhibition.2019 年骨髓纤维化:超越 JAK2 抑制。
Blood Cancer J. 2019 Sep 11;9(9):74. doi: 10.1038/s41408-019-0236-2.