费城阴性的慢性髓增多性肿瘤与巨大的共病负担有关，包括心血管疾病的增加风险。最近，慢性炎症被认为是慢性髓增多性肿瘤克隆进化和疾病进展的驱动力，同时也可能对早期动脉粥样硬化的发展产生影响。由于慢性炎症、动脉粥样硬化和动脉粥样硬化血栓形成在慢性髓增多性肿瘤中普遍存在，并且我们以前已经显示氧化应激基因在该疾病中明显上调，我们假设与动脉粥样硬化发展相关的基因也可能高度异常调节。我们在血红细胞增多性血小板增多性血小板造血生物组（ET；n = 19），红细胞增多性真性红细胞增多症（PV；n = 41）或原发性骨髓纤维化（PMF；n = 9）患者中使用全血基因表达谱进行了研究，我们首次报告了多个动脉粥样硬化基因的异常表达。在84个动脉粥样硬化基因中，分别在ET，PV或PMF患者中有45、56和46个基因异常调节。此外，BCL2L1、MMP1、PDGFA、PTGS1和THBS4从ET到PV再到PMF逐渐显著上调，而BCL2逐渐显著下调（所有FDR < 0.05）。我们首次展示了慢性髓增多性肿瘤中动脉粥样硬化基因的大规模异常调节，很可能反映了该疾病中的炎症状态与体内白细胞、血小板和内皮细胞的活化密切相关，这些细胞在动脉粥样硬化进程中起到关键作用。© 2023 The Authors. 由John Wiley＆Sons Ltd发表的《欧洲血液学杂志》。

The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are associated with a huge comorbidity burden, including an increased risk of cardiovascular diseases. Recently, chronic inflammation has been suggested to be the driving force for clonal evolution and disease progression in MPN but also potentially having an impact upon the development of accelerated (premature) atherosclerosis.Since chronic inflammation, atherosclerosis, and atherothrombosis are prevalent in MPNs and we have previously shown oxidative stress genes to be markedly upregulated in MPNs, we hypothesized that genes linked to development of atherosclerosis might be highly deregulated as well.Using whole blood gene expression profiling in patients with essential thrombocythemia (ET; n = 19), polycythemia vera (PV; n = 41), or primary myelofibrosis (PMF; n = 9), we herein for the first time report aberrant expression of several atherosclerosis genes.Of 84 atherosclerosis genes, 45, 56, and 46 genes were deregulated in patients with ET, PV, or PMF, respectively. Furthermore, BCL2L1, MMP1, PDGFA, PTGS1, and THBS4 were progressively significantly upregulated and BCL2 progressively significantly downregulated from ET over PV to PMF (all FDR <0.05).We have for the first time shown massive deregulation of atherosclerosis genes in MPNs, likely reflecting the inflammatory state in MPNs in association with in vivo activation of leukocytes, platelets, and endothelial cells being deeply involved in the atherosclerotic process.© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.