Wang Yingying, Zuo Xuelan
Department of Hematology, Zhongnan Hospital of Wuhan University, 169 Donghu Road, Wuchang, Wuhan, Hubei 430071, PR China.
Cytokine X. 2019 Mar 27;1(1):100005. doi: 10.1016/j.cytox.2019.100005. eCollection 2019 Mar.
Classical myeloproliferative neoplasms (MPN) include polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). MPN has been defined as a chronic inflammation-driven tumor model. It is clear that there is a close link between chronic inflammation and MPN pathogenesis. Several studies have demonstrated cytokine profiles in MPN patients. Other studies have used cell lines or animal models aiming to clarify the underlying mechanism of cytokines in the pathogenesis of MPN. However, important questions remain: (1) among all these cytokines, which are more predictive? and (2) which are more critical? In this review, we summarize cytokines that have been investigated in MPN and highlight several cytokines that may be more significant in MPN. We suggest that cytokines are more critical in PMF than PV or ET. These cytokines include IL-1β, TNF-α, IL-6, IL-8, VEGF, PDGF, IFNs and TGF-β, all of which should be more closely investigated in MPN. Based on our extensive literature search, several key factors have emerged in our understanding of MPN: first, TNF-α could correlate with MPN progression including PMF, PV and ET. IL-1β plays a role in PMF progression, while it showed no relation with PV or ET. Second, IL-8 could be a prognostic factor for PMF, and IL-6 could be important for MPN progression. Third, VEGF and PDGF play an indirect role in MPN development and their inhibitors could be effective. Fourth, different subtypes of IFNs could have different effects in MPN. Finally, TGF-β is closely linked to MF, although the data are inconsistent. Agents that have targeted these cytokines described above are already in clinical trials, and some of them have even been used to treat MPN patients. Taken together, it will be critical to continue to investigate the precise role of these cytokines in the pathogenesis and progression of MPN.
经典型骨髓增殖性肿瘤（MPN）包括真性红细胞增多症（PV）、原发性血小板增多症（ET）和原发性骨髓纤维化（PMF）。MPN被定义为一种慢性炎症驱动的肿瘤模型。很明显，慢性炎症与MPN发病机制之间存在密切联系。多项研究已证实MPN患者的细胞因子谱。其他研究则使用细胞系或动物模型，旨在阐明细胞因子在MPN发病机制中的潜在机制。然而，重要问题依然存在：（1）在所有这些细胞因子中，哪些更具预测性？以及（2）哪些更关键？在本综述中，我们总结了在MPN中已被研究的细胞因子，并强调了几种在MPN中可能更具重要意义的细胞因子。我们认为细胞因子在PMF中比在PV或ET中更关键。这些细胞因子包括白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）、血管内皮生长因子（VEGF）、血小板衍生生长因子（PDGF）、干扰素（IFNs）和转化生长因子-β（TGF-β），所有这些在MPN中都应进行更深入的研究。基于我们广泛的文献检索，在我们对MPN的认识中出现了几个关键因素：首先，TNF-α可能与MPN进展相关，包括PMF、PV和ET。IL-1β在PMF进展中起作用，而它与PV或ET无关。其次，IL-8可能是PMF的一个预后因素，而IL-6对MPN进展可能很重要。第三，VEGF和PDGF在MPN发展中起间接作用，其抑制剂可能有效。第四，不同亚型的IFNs在MPN中可能有不同作用。最后，TGF-β与MF密切相关，尽管数据并不一致。针对上述这些细胞因子的药物已进入临床试验，其中一些甚至已用于治疗MPN患者。综上所述，继续研究这些细胞因子在MPN发病机制和进展中的精确作用至关重要。
