Unità Funzionale di Ematologia, Dipartimento di Area Critica, Università degli Studi, Florence, Italy.
Intern Emerg Med. 2010 Jun;5(3):177-84. doi: 10.1007/s11739-009-0319-3. Epub 2009 Sep 30.
The classic myeloproliferative neoplasms (MPNs) include polycythemia vera and essential thrombocythemia; their molecular basis has been described only recently with the demonstration of recurrent mutations in JAK2 or MPL. While life expectancy may not be significantly shortened, arterial and venous thrombosis constitute the major causes of morbidity and mortality, together with disease evolution to myelofibrosis or transformation to acute leukemia. Therapy is currently aimed at reducing the rate of thrombosis without increasing the risk of hematologic transformation by inappropriate exposure to cytotoxic drugs. Nevertheless, the mechanism(s) finally responsible for the increased thrombotic tendency have not been clearly elucidated, although risk factors for thrombosis have been identified, and are currently employed for stratifying patients to the most appropriate therapeutic options. Abnormalities of blood cells, activation of neutrophils and platelets, and a hypercoagulability state, can all act in conjunction to lead to thrombosis. Intriguing data also point to the JAK2V617F mutation as both a marker and a mechanism for thrombosis. Better knowledge in the pathophysiology of these disorders, and the introduction of molecularly targeted drugs in clinical trials, anticipate the possibility of more specific and efficacious treatment of classic MPN, particularly as concerns the reduction of risk associated with vascular events.
经典的骨髓增殖性肿瘤（MPN）包括真性红细胞增多症和原发性血小板增多症；它们的分子基础最近才被描述出来，证明了 JAK2 或 MPL 反复发生突变。虽然预期寿命可能不会显著缩短，但动脉和静脉血栓形成是发病率和死亡率的主要原因，加上疾病向骨髓纤维化或转化为急性白血病的演变。目前的治疗方法旨在降低血栓形成的速度，同时避免因不当暴露于细胞毒性药物而增加血液学转化的风险。然而，导致血栓形成倾向增加的机制尚未明确阐明，尽管已经确定了血栓形成的危险因素，并目前用于将患者分层为最合适的治疗选择。血细胞异常、中性粒细胞和血小板的激活以及高凝状态都可能共同作用导致血栓形成。有趣的数据也表明 JAK2V617F 突变既是血栓形成的标志物，也是其机制。对这些疾病病理生理学的更好认识，以及分子靶向药物在临床试验中的引入，预示着经典 MPN 的治疗可能更加具体和有效，特别是在降低与血管事件相关的风险方面。
