Department of Hematology, Roskilde Hospital, University of Copenhagen, Køgevej 7-13, Roskilde, Denmark.
Blood. 2012 Apr 5;119(14):3219-25. doi: 10.1182/blood-2011-11-394775. Epub 2012 Feb 7.
The morbidity and mortality of patients with the chronic Philadelphia-negative myeloproliferative neoplasms (MPNs), essential thrombocythemia, polycythemia vera, and primary myelofibrosis are mainly caused by cardiovascular diseases, thrombohemorrhagic complications, and bone marrow failure because of myelofibrosis and leukemic transformation. In the general population, chronic inflammation is considered of major importance for the development of atherosclerosis and cancer. MPNs are characterized by a state of chronic inflammation, which is proposed to be the common denominator for the development of "premature atherosclerosis," clonal evolution, and second cancer in patients with MPNs. Chronic inflammation may both initiate clonal evolution and catalyze its expansion from early disease stage to the myelofibrotic burnt-out phase. Furthermore, chronic inflammation may also add to the severity of cardiovascular disease burden by accelerating the development of atherosclerosis, which is well described and recognized in other chronic inflammatory diseases. A link between chronic inflammation, atherosclerosis, and second cancer in MPNs favors early intervention at the time of diagnosis (statins and interferon-α2), the aims being to dampen chronic inflammation and clonal evolution and thereby also diminish concurrent disease-mediated chronic inflammation and its consequences (accelerated atherosclerosis and second cancer).
慢性费城阴性骨髓增殖性肿瘤（MPN）患者的发病率和死亡率主要归因于心血管疾病、血栓出血并发症以及骨髓纤维化和白血病转化导致的骨髓衰竭，这些疾病包括原发性血小板增多症、真性红细胞增多症和原发性骨髓纤维化。在普通人群中，慢性炎症被认为是动脉粥样硬化和癌症发展的主要因素。MPN 以慢性炎症状态为特征，这被认为是“过早动脉粥样硬化”、克隆进化以及 MPN 患者继发第二癌症发展的共同基础。慢性炎症可能启动克隆进化，并促进其从早期疾病阶段向骨髓纤维化耗竭阶段扩展。此外，慢性炎症还可能通过加速动脉粥样硬化的发展，加重心血管疾病负担，这种情况在其他慢性炎症性疾病中得到了很好的描述和认识。MPN 中慢性炎症、动脉粥样硬化和第二癌症之间的联系支持在诊断时进行早期干预（他汀类药物和干扰素-α2），其目的是抑制慢性炎症和克隆进化，从而减少同时存在的疾病介导的慢性炎症及其后果（加速的动脉粥样硬化和第二癌症）。
