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  • buy Erastin Finally it is highly interesting to note

    2019-05-31

    Finally, it is highly interesting to note that human endogenous retroviruses have been suggested to play a role in the etiology of both MS and MPN [7,9]. Supporting this notion, both MS and MPN are treated with type 1 interferons, which have very potent antiviral and immunomodulating effects. Indeed, IFN-alpha2 is able to induce sustained complete hematological remissions with normalization of the bone marrow even after discontinuation of interferon-alpha2 for up to three years. Accordingly, endogenous human retrovirus has most recently been proposed to be involved in the pathogenesis of MPNs [7]. In conclusion, we report for the first time the unusual concurrence of MS and MPNs in five patients from a localized geographic area in Denmark. This observation calls attention to potential environmental factors and/or previously unrecognized genetic factors predisposing these patients to both MS and MPN. It also raises the possibility that MPNs might be underdiagnosed in MS patients, since especially ET and PV patients can have discrete symptoms. This might contribute to the increased risk of both venous and arterial thrombosis in MS patients [10]. In the context that IFN-alpha and -beta interfere with virus replication it is of interest to consider if chronic buy Erastin – possibly elicited by virus infection – may trigger and drive MS and MPNs [7]. The susceptibility to these diseases may be dependent upon the individual haplotype which may be shared by both diseases. Further studies are needed to clarify if an association between MS and MPNs indeed exists in the Danish MS/MPN population or in distinct areas and – if so – to elucidate common factors which might explain the concurrence of two rare diseases, including environmental (e.g. chronic inflammation – a role of human endogenous retrovirus?) or genetic factors (e.g. a common JAK2 haplotype) predisposing the patients to both diseases.
    Introduction Acquired JAK2V617F somatic mutation is a hallmark of Philadelphia negative myeloproliferative neoplasm (MPN) [1,2]. In myelodysplastic syndromes (MDS), JAK2V617F mutation is seen in less than 5% of the cases [3]. Both 2001 and 2008 WHO classifications include among myelodysplastic/myeloproliferative (MDS/MPN) overlap syndromes [4] a provisional entity, refractory anemia with ringed sideroblasts associated with sustained thrombocytosis (RARS-T) that appears to have a relatively favorable prognosis [5] especially if JAK2V617F mutation, detected in about 60% of the cases, is present [3]. Apart from RARS-T, however, the impact of JAK2V617F mutation in MDS remains unknown [6–8]. We conducted a retrospective study of MDS patients with JAK2V617F mutation, after exclusion of RARS-T cases, where patients were compared with matched unmutated MDS without JAK2V617F mutation.
    Materials/methods
    Results Data from 132 MDS patients with known JAK2V617F mutation status were collected in 19 centers of the FIM and GFM, including 37 JAK2V617F positive (JAK2+) and 95 JAK2V617F negative (JAK2−) cases. Their main clinical and laboratory features are presented in Table 1. The JAK2V617F mutation burden was available in only 7 patients, showing a median level of 16% (range, 1–50%). There were no significant differences between JAK2+ and JAK2− cases in terms of age, gender, hemoglobin level, WHO 2008 classification, cytogenetic findings and IPSS. In JAK2+ patients, the white blood cells (WBC) count, absolute neutrophil count (ANC), platelet count and mean corpuscular volume (MCV) were significantly higher, while the marrow blast percentage was significantly lower than in JAK2− cases. Treatments used (Table 1) were similar in both patient groups, especially with regards to erythropoietic stimulating agents, chemotherapy and hypomethylating agents. Seventeen JAK2+ (45%) versus 36 (37.8%) JAK2− patients were red blood cell transfusion-dependent (p=.77). Median follow up was 44 months (range 18–349) in JAK2+ and 69 months (range 32–185) in JAK2− patients (p=.95). OS was significantly longer in JAK2+ patients (median not reached) than in JAK2− patients (median 66 months) (p=.011) (Fig. 1). The estimated 5-year OS was 86% in JAK2+ patients versus 57% in JAK2− patients. The 10 year cumulative incidence of AML progression was significantly lower in JAK2+ (20%) than in JAK2− patients (47%) (p<.001).