Mutational profiling, usually by targeted next-generation sequencing, is increasingly performed on patients with myeloproliferative neoplasm-associated myelofibrosis (MF), whether primary (PMF) or post-polycythemia vera/essential thrombocythemia (post-PV/ET MF). "Driver" mutations in JAK2, MPL and indels in CALR underlie the vast majority of cases of PMF and post-ET MF; the remainder (≈ 10%) lack identifiable driver mutations, but other clonal markers are usually detectable. Nearly all patients with post-PV MF carry activating JAK2 mutations. In both PMF and post-ET MF, type 1/-like CALR mutations confer a favorable prognosis. Since both type 1/-like and type 2/-like CALR mutations have essentially the same functional consequence, this is a subject of intense research. Additional, "non-driver" mutations, mostly affecting genes encoding epigenetic modifiers or spliceosome components, e.g., ASXL1, EZH2, TET2, DNMT3A, SRSF2 and U2AF1, are frequently found; some of these are associated with inferior survival and have been incorporated into prognostic models. Some mutations, e.g., IDH1/2, are relatively infrequent in chronic phase but are substantially more common in blast phase, and are now therapeutically targetable. While mutational information does not currently influence choice of drug therapy in chronic-phase MF, the presence of a "high molecular risk" genotype is now routinely taken into account for transplant decision-making.

中文翻译：

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骨髓纤维化的突变谱：对管理的影响。

无论是原发性（PMF）还是真性红细胞增多症/实质性血小板增多症（PV / ET MF之后），通常都通过靶向下一代测序进行突变谱分析，通常是针对与骨髓增生性肿瘤相关的骨髓纤维化（MF）的患者进行的。在PMF和ET后MF的绝大多数病例中，JAK2，MPL和CALR中indels的“驱动基因”突变；其余（≈10％）缺乏可识别的驱动突变，但通常可以检测到其他克隆标记。几乎所有患有PV MF后的患者均具有激活的JAK2突变。在PMF和ET后MF中，1 /型样CALR突变均具有良好的预后。由于1型/样和2型样的CALR突变具有基本相同的功能结果，因此这是一个深入研究的主题。其他“非驾驶员”突变，经常发现主要影响编码表观遗传修饰子或剪接体成分的基因，例如ASXL1，EZH2，TET2，DNMT3A，SRSF2和U2AF1。其中一些与生存期较低有关，并已纳入预后模型。一些突变，例如IDH1 / 2，在慢性期相对不常见，而在胚芽期则更为常见，现在可以治疗靶向。虽然突变信息目前尚不影响慢性期MF的药物治疗选择，但现在对于移植决策通常要考虑“高分子风险”基因型的存在。其中一些与生存期较低有关，并已纳入预后模型。一些突变，例如IDH1 / 2，在慢性期相对不常见，而在胚芽期则更为常见，现在可以治疗靶向。虽然突变信息目前尚不影响慢性期MF的药物治疗选择，但现在对于移植决策通常要考虑“高分子风险”基因型的存在。其中一些与生存期较低有关，并已纳入预后模型。一些突变，例如IDH1 / 2，在慢性期相对不常见，而在胚芽期则更为常见，现在可以治疗靶向。虽然突变信息目前尚不影响慢性期MF的药物治疗选择，但现在对于移植决策通常要考虑“高分子风险”基因型的存在。