The term myeloproliferative disorders was first proposed by

The term “myeloproliferative disorders” was first proposed by William Dameshek in 1951. With the discovery of the Philadelphia chromosome, myeloproliferative disorders were classified into two groups: BCR-ABL positive chronic myeloid leukemia (CML) and BCR-ABL negative chronic myeloproliferative disorders (CMD) [1]. The latter was replaced by the name myeloproliferative neoplasms (MPN), which is more representative of the clonal features for this disease group. It includes several subtypes: PV, ET, PMF, chronic neutrophilic leukemia (CNL), unclassified myeloproliferative neoplasms (MPN-U) and chronic eosinophilic leukemia, not otherwise specified (CEL-NOS) [2]. The first three entities (PV, ET and PMF) represent classical MPN. Epidemiology of MPN in Europe and USA shows the incidence of MPN is about 2–3/100,000, and an increased tendency has been observed in the last 10 years [3], [4]. Many advances have been made in MPN pathogenesis and treatment since the discovery of the JAK2V617F mutation as an MPN disease marker in 2005 [5], [6]. Soon after, other gene mutations were identified in MPN including mutations in the myeloproliferative leukemia protein (MPL) and calreticulin (CALR) [7], [8], [9], [10]. Emerging results from clinical surveys of gene mutations in MPN patients and transgenic animal model studies revealed that these gene mutations could be driven factors for the clonal Dynorphin A in developing MPN [11], [12]. Ruxolitinib, a JAK-inhibitor, has been used for PMF patients as a standard treatment, and it has been investigated in PV or ET patients with hydroxycarbamide (HC) failure/intolerance as a second line treatment [13]. However, other factors could be involved in classical MPN pathogenesis. Hasselbalch proposed the idea that chronic inflammation plays a critical role in MPN development [14]. This was later confirmed by many studies that demonstrated the critical role of inflammation in the initiation and progression of MPN; it has been proposed that MPN could be an inflammation-driven tumor model [15], [16], [17], [18], [19]. Clinical surveys have focused on inflammatory mediators such as cytokines, and many cytokines have been evaluated in blood serum or bone marrow plasma from MPN patients by different MPN centers [20], [21]. Furthermore, IFN-α has been used in treating MPN effectively for more than fifty years and has a stable therapeutic status in MPN management even with the common usage of Ruxolitinib [22]. Altogether, these studies suggest that there is a close relationship between MPN and inflammation, though it is still not clear whether inflammation or gene mutation is the trigger for MPN. Tumor development is always a multi-step process that involves cooperating effects of both intrinsic and extrinsic factors. We, therefore, suggest that both gene mutation and chronic inflammation are critical in the development of MPN. Immunotherapy is very popular, especially chimeric antigen receptors T (CART) cell therapy, which has revolutionized tumor treatment not only in hematology malignancies but also in solid tumors [23]. For MPN, it is possible to use gene-modified T cells to kill the MPN clone, which would exert an immunomodulating role by balancing inflammatory cytokine levels. The latter could control the disease. At the very least, cytokine-directed immunotherapy for MPN could be a new treatment strategy in the future. In this review, we summarize experimental results of cytokine profiles in MPN and potential clinical applications of cytokines in treating MPN.