Blood Cancer Research Group, Centre for Cancer Research and Cell Biology, Queens University Belfast, Belfast, UK.
Centre for Medical Education, School of Medicine, Dentistry and Biomedical Sciences, Queens University Belfast, Belfast, UK.
J Cell Mol Med. 2017 Sep;21(9):1660-1667. doi: 10.1111/jcmm.13095. Epub 2017 Jul 4.
A decade on from the description of JAK2 V617F, the MPNs are circumscribed by an increasingly intricate landscape. There is now evidence that they are likely the result of combined genetic dysregulation, with several mutated genes involved in the regulation of epigenetic mechanisms. Epigenetic changes are not due to a change in the DNA sequence but are reversible modifications that dictate the way in which genes may be expressed (or silenced). Among the epigenetic mechanisms, DNA methylation is probably the best described. Currently known MPN-associated mutations now include JAK2, MPL, LNK, CBL, CALR, TET2, ASXL1, IDH1, IDH2, IKZF1 and EZH2. Enhancing our knowledge about the mutation profile of patients may allow them to be stratified into risk groups which would aid clinical decision making. Ongoing work will answer whether the use of epigenetic therapies as alterative pathway targets in combination with JAK inhibitors may be more effective than single agent treatment.
在描述 JAK2 V617F 十周年之际，MPNs 的范围被越来越复杂的景观所限定。现在有证据表明，它们可能是基因调控失调的结果，涉及几个调节表观遗传机制的突变基因。表观遗传变化不是由于 DNA 序列的改变，而是决定基因表达（或沉默）方式的可逆修饰。在表观遗传机制中，DNA 甲基化可能是描述得最好的。目前已知的与 MPN 相关的突变包括 JAK2、MPL、LNK、CBL、CALR、TET2、ASXL1、IDH1、IDH2、IKZF1 和 EZH2。提高我们对患者突变谱的认识，可能使他们能够分层为风险组，这将有助于临床决策。正在进行的工作将回答是否使用表观遗传学治疗作为 JAK 抑制剂的替代途径靶点与单一药物治疗相比是否更有效。
