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  • br Role of the funding source br Introduction

    2019-05-29


    Role of the funding source
    Introduction Myeloproliferative neoplasms (MPNs) are stem-cell-derived disorders that cause overproduction of one or more of the formed elements of the blood. MPNs include chronic myelogenous leukemia (CML) and the Philadelphia-negative MPNs: polycythemia vera (PV), essential thrombocythemia (ET), primary myelofibrosis (PMF) and unclassifiable MPN (MPN-U) [1]. A gain-of-function s1p receptor in the gene for Janus kinase 2 (JAK2), the JAK2 V617F mutation, is found in the majority of patients with PV and about half of patients with ET and PMF. The etiology of MPNs is unknown, but an increased risk of MPNs has been found in patients with a family history of MPNs, prior autoimmune and/or inflammatory conditions and exposure to certain chemicals [2]. Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system of unknown etiology. MS can be divided into relapsing-remitting, primary progressive and secondary progressive MS, depending on the clinical course [3]. Here we describe four cases of MS-patients that subsequently developed MPNs and one case of a MPN-patient that developed MS. All five patients were referred to our centers, in the period of 2007–2012. Two of the patients were diagnosed with PV, the third with MPN-U, the fourth with ET and the fifth with PMF. All patients were diagnosed with MS according to the McDonald diagnostic criteria and with MPNs according to the WHO criteria [1,3].
    Case stories Case reports with patient characteristics are summarized in Table 1.
    Discussion The concurrence of MS and MPN in our series of patients is unusually high with four patients in the Roskilde MPN-population alone. The annual incidence rate of MS in Denmark is about 4.44 per 100,000 population, being 37% higher in females than males [4]. The true incidence of MPNs in Denmark is unknown but is estimated to be approximately 0.5–1.5 per 100,000 per year for ET and PV, respectively, and about 0.5 per 100,000 per year for PMF. Only one case report has previously described the concurrence of a Philadelphia-negative MPN and MS, which developed during the course of ET [5]. A potential link between MS and myeloid cancer has not been previously recognized. A population-based study from 2010 found no association between previous MS diagnosis and development of MPNs [6]. For these reasons, the concurrence of four patients with both MS and MPN in the Roskilde MPN-population, and an additional patient in another hematological department in the same geographic area, is certainly highly unexpected. The association between chronic inflammation and subsequent cancer is well established, and chronic inflammation is thought to have a role in both the initiation and promotion of neoplasms [7]. s1p receptor MS is a relapsing inflammatory disease of the central nervous system that leads to damage of nerves and axons. Dysregulation of the immune system leads to activation of autoreactive lymphocytes that migrate across the blood-brain barrier and initiate the production of pro-inflammatory cytokines [8]. Chronic inflammation has been hypothesized to play a role in triggering clonal evolution in MPNs [7]. Therefore, it is intriguing to consider if chronic inflammation in our five MS patients may be involved in the development of their MPNs. In this context it is important to note that all our patients were relatively newly diagnosed – four being in the early stage (ET/PV) in the biological continuum, and one patient diagnosed with myelofibrosis. Many patients with MPNs have most likely had their cancer for several years before diagnosis, elevated leukocyte and platelet counts being considered “reactive”. Accordingly, the inflammation drive – having potentially triggered the two illnesses – may have been ongoing for several years before the clinical diagnosis of MPNs and MS. Other possibilities to consider in regard to the concurrence of MPNs and MS are hematological side effects of the MS treatment, environmental or genetic factors.