细胞因子在骨髓纤维化的发生和进展中的作用。

The role of cytokines in the initiation and progression of myelofibrosis.

机构信息

Department of Hematology, Roskilde Hospital University of Copenhagen, Køgevej 7-13, 4000 Roskilde, Denmark.

出版信息

Cytokine Growth Factor Rev. 2013 Apr;24(2):133-45. doi: 10.1016/j.cytogfr.2013.01.004. Epub 2013 Feb 13.

DOI:10.1016/j.cytogfr.2013.01.004

Abstract

Myelofibrosis (MF) is a life-threatening blood cancer characterized by progressive bone marrow fibrosis, splenomegaly, cytopenias, and debilitating constitutional symptoms. Abnormal expression and activity of a number of proinflammatory cytokines are associated with MF, in which immune dysregulation is pronounced as evidenced by dysregulation of several immune and inflammation genes. The discovery of the Janus kinase 2 (JAK2) V617F mutation has led to the development of a number of JAK1/2 inhibitors in the treatment of MF and similar neoplasms. Here, the role of cytokines in MF initiation and progression is discussed, the impact of current therapies is reviewed, and new combination therapies are proposed, such as JAK1/2 inhibitors with interferons, statins, and epigenetic modifiers for patients with MF and related neoplasms.

摘要

骨髓纤维化（MF）是一种危及生命的血液癌，其特征为进行性骨髓纤维化、脾肿大、细胞减少症和使人虚弱的全身症状。许多促炎细胞因子的异常表达和活性与 MF 有关，其中免疫失调明显，证据为几种免疫和炎症基因的失调。Janus 激酶 2（JAK2）V617F 突变的发现导致了许多 JAK1/2 抑制剂在 MF 和类似肿瘤的治疗中的发展。在这里，讨论了细胞因子在 MF 起始和进展中的作用，回顾了当前治疗方法的影响，并提出了新的联合治疗方法，例如 JAK1/2 抑制剂与干扰素、他汀类药物和表观遗传修饰剂联合用于 MF 和相关肿瘤患者。