Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Best Pract Res Clin Haematol. 2009 Dec;22(4):489-94. doi: 10.1016/j.beha.2009.08.006.
In recent years, a series of studies have provided genetic insight into the pathogenesis of myeloproliferative neoplasms (MPNs). It is now known that JAK2V617F mutations are present in 90% of patients with polycythaemia vera (PV), 60% of patients with essential thrombocytosis (ET) and 50% of patients with myelofibrosis (MF). Despite the high prevalence of JAK2V617F mutations in these three myeloid malignancies, several questions remain. For example, how does one mutation contribute to the pathogenesis of three clinically distinct diseases, and how do some patients develop these diseases in the absence of a JAK2V617F mutation? Single nucleotide polymorphisms at various loci and somatic mutations, such as those in MPLW515L/K, TET2 and in exon 12 of JAK2, may also contribute to the pathogenesis of these MPNs. There are likely additional germline and somatic genetic factors important to the MPN phenotype. Additional studies of large MPN and control cohorts with new techniques will help identify these factors.
近年来，一系列研究为骨髓增殖性肿瘤（MPN）的发病机制提供了遗传学见解。现在已知，90%的真性红细胞增多症（PV）患者、60%的原发性血小板增多症（ET）患者和 50%的骨髓纤维化（MF）患者存在 JAK2V617F 突变。尽管这三种髓系恶性肿瘤中 JAK2V617F 突变的患病率很高，但仍存在一些问题。例如，一个突变如何导致三种临床表现截然不同的疾病，以及为什么一些患者在没有 JAK2V617F 突变的情况下会患上这些疾病？在不同位置的单核苷酸多态性和体细胞突变，如 MPLW515L/K、TET2 和 JAK2 外显子 12 中的突变，也可能有助于这些 MPN 的发病机制。可能还有其他与 MPN 表型相关的种系和体细胞遗传因素。使用新技术对大型 MPN 和对照队列进行更多研究将有助于确定这些因素。
