Zhou Amy, Afzal Amber, Oh Stephen T
Division of Hematology, Washington University in St. Louis School of Medicine, 660 S. Euclid Ave, Campus Box 8125, St. Louis, MO, 63110, USA.
Curr Hematol Malig Rep. 2017 Oct;12(5):397-405. doi: 10.1007/s11899-017-0401-2.
The prognosis for patients with Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is highly variable. All Ph-negative MPNs carry an increased risk for thrombotic complications, bleeding, and leukemic transformation. Several clinical, biological, and molecular prognostic factors have been identified in recent years, which provide important information in guiding management of patients with Ph-negative MPNs. In this review, we critically evaluate the recent published literature and discuss important new developments in clinical and molecular factors that impact survival, disease transformation, and thrombosis in patients with polycythemia vera, essential thrombocythemia, and primary myelofibrosis.
Recent studies have identified several clinical factors and non-driver mutations to have prognostic impact on Ph-negative MPNs independent of conventional risk stratification and prognostic models. In polycythemia vera (PV), leukocytosis, abnormal karyotype, phlebotomy requirement on hydroxyurea, increased bone marrow fibrosis, and mutations in ASXL1, SRSF2, and IDH2 were identified as additional adverse prognostic factors. In essential thrombocythemia (ET), JAK2 V617F mutation, splenomegaly, and mutations in SH2B3, SF3B1, U2AF1, TP53, IDH2, and EZH2 were found to be additional negative prognostic factors. Bone marrow fibrosis and mutations in ASXL1, SRSF2, EZH2, and IDH1/2 have been found to be additional prognostic factors in primary myelofibrosis (PMF). CALR mutations appear to be a favorable prognostic factor in PMF, which has not been clearly demonstrated in ET. The prognosis for patients with PV, ET, and PMF is dependent upon the presence or absence of several clinical, biological, and molecular risk factors. The significance of additional risk factors identified in these recent studies will need further validation in prospective studies to determine how they may be best utilized in the management of these disorders.
费城染色体（Ph）阴性骨髓增殖性肿瘤（MPN）患者的预后差异很大。所有Ph阴性MPN患者发生血栓并发症、出血和白血病转化的风险均增加。近年来已确定了多种临床、生物学和分子预后因素，这些因素为指导Ph阴性MPN患者的管理提供了重要信息。在本综述中，我们批判性地评估了最近发表的文献，并讨论了影响真性红细胞增多症、原发性血小板增多症和原发性骨髓纤维化患者生存、疾病转化和血栓形成的临床和分子因素的重要新进展。
最近的研究已确定，一些临床因素和非驱动基因突变对Ph阴性MPN具有预后影响，独立于传统的风险分层和预后模型。在真性红细胞增多症（PV）中，白细胞增多、核型异常、羟基脲治疗下的放血需求、骨髓纤维化增加以及ASXL1、SRSF2和IDH2基因突变被确定为额外的不良预后因素。在原发性血小板增多症（ET）中，JAK2 V617F突变、脾肿大以及SH2B3、SF3B1、U2AF1、TP53、IDH2和EZH2基因突变被发现是额外的阴性预后因素。骨髓纤维化以及ASXL1、SRSF2、EZH2和IDH1/2基因突变已被发现是原发性骨髓纤维化（PMF）的额外预后因素。CALR突变似乎是PMF的一个有利预后因素，这在ET中尚未得到明确证实。PV、ET和PMF患者的预后取决于多种临床、生物学和分子风险因素的存在与否。这些最新研究中确定的其他风险因素的意义需要在前瞻性研究中进一步验证，以确定如何在这些疾病的管理中最佳利用它们。
