Center for the Study of Myelofibrosis. Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, 27100, Italy.
Biotechnology Research Area, IRCCS Policlinico S. Matteo Foundation, Pavia, 27100, Italy.
Am J Hematol. 2016 Jul;91(7):709-13. doi: 10.1002/ajh.24388. Epub 2016 May 26.
Myeloproliferative neoplasm (MPN)-associated myelofibrosis is a clonal, neoplastic disorder of the hematopoietic stem cells, in which inflammation and immune dysregulation play an important role. Extracellular nicotinamide phosphoribosyltransferase (eNAMPT), also known as visfatin, is a cytokine implicated in a number of inflammatory and neoplastic diseases. Here plasma levels of eNAMPT in patients with MPN-associated myelofibrosis and their effects on disease phenotype and outcomes were examined. The concordance of eNAMPT levels with the marker of general inflammation high-sensitivity C-reactive protein (hs-CRP) was also studied. A total of 333 MPN-associated myelofibrosis patients (187 males and 146 females) and 31 age- and gender-matched normal-weight healthy subjects were enrolled in the study main body. Levels of eNAMPT and hs-CRP were simultaneously assayed in 209 MPN-associated myelofibrosis patients. Twenty-four polycythemia vera or essential thrombocythemia patients were used as controls. eNAMPT was over expressed in MPN-associated myelofibrosis, and eNAMPT expression was correlated with higher white blood cell count, higher hemoglobin, and higher platelet count, suggesting that eNAMPT is an indispensable permissive agent for myeloproliferation of MPN-associated myelofibrosis. The lack of correlation between eNAMPT and hs-CRP revealed that eNAMPT in MPN-associated myelofibrosis does not behave as a canonical inflammatory cytokine. In addition, higher levels of eNAMPT predicted longer time to blast transformation, and protected against progression toward thrombocytopenia and large splenomegaly. In conclusion, in MPN-associated myelofibrosis high levels of eNAMPT mark the myeloproliferative potential and, at variance with a high number of cancers, are protective against disease progression. Am. J. Hematol. 91:709-713, 2016. © 2016 Wiley Periodicals, Inc.
骨髓增生性肿瘤（MPN）相关的骨髓纤维化是造血干细胞的克隆性、肿瘤性疾病，其中炎症和免疫失调起着重要作用。细胞外烟酰胺磷酸核糖基转移酶（eNAMPT），也称为内脏脂肪素，是一种细胞因子，涉及许多炎症和肿瘤疾病。本研究旨在检测 MPN 相关骨髓纤维化患者血浆中 eNAMPT 水平及其对疾病表型和预后的影响，并研究其与炎症标志物高敏 C 反应蛋白（hs-CRP）的一致性。本研究共纳入 333 名 MPN 相关骨髓纤维化患者（187 名男性和 146 名女性）和 31 名年龄和性别匹配的正常体重健康对照者。同时检测 209 名 MPN 相关骨髓纤维化患者的 eNAMPT 和 hs-CRP 水平。24 名真性红细胞增多症或原发性血小板增多症患者作为对照组。MPN 相关骨髓纤维化患者中 eNAMPT 表达升高，eNAMPT 表达与较高的白细胞计数、较高的血红蛋白和较高的血小板计数相关，提示 eNAMPT 是 MPN 相关骨髓纤维化骨髓增生的必需许可因子。eNAMPT 与 hs-CRP 之间缺乏相关性表明，MPN 相关骨髓纤维化中的 eNAMPT 不表现为经典的炎症细胞因子。此外，较高的 eNAMPT 水平预示着向白血病转化的时间延长，并能防止向血小板减少症和大脾肿大进展。总之，在 MPN 相关骨髓纤维化中，高水平的 eNAMPT 标志着骨髓增生的潜能，与许多癌症不同，它对疾病进展具有保护作用。Am J Hematol. 91:709-713, 2016. © 2016 Wiley Periodicals, Inc.
