Department of Pathology and Laboratory Medicine, UConn Health, Farmington, Connecticut, USA.
Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Int J Lab Hematol. 2023 Dec;45(6):839-844. doi: 10.1111/ijlh.14184. Epub 2023 Oct 22.
The blast phase of BCR::ABL1-negative myeloproliferative neoplasm (MPN-BP) represents the final stage of the disease, which is complicated by complex genomic alterations. These alterations result from sequence changes in genetic material (DNA, RNA) and can lead to either a gain or loss of function of encoded proteins, such as adaptor proteins, enzymes, components of spliceosomes, cell cycle checkpoints regulators, transcription factors, or proteins in cell signaling pathways. Interference at various levels, including transcription, translation, and post-translational modification (such as methylation, dephosphorylation, or acetylation), can contribute to these alterations. Mutated genes such as ASXL1, EZH2, IDH1, IDH2, TET2, SRSF2, U2AF1, TP53, NRAS, KRAS, PTPN11, SH2B3/LNK, and RUNX1 play active roles at different stages of genetic material expression, modification, and protein function manipulation in MPNs. These mutations are also correlated with, and can contribute to, the progression of MPN-BP. In this review, we summarize their common mutational profiles, functions, and associations with progression of MPN-BP.
:ABL1 阴性骨髓增殖性肿瘤（MPN-BP）的急变期代表疾病的终末阶段，其特点是复杂的基因组改变。这些改变源于遗传物质（DNA、RNA）的序列变化，可能导致编码蛋白的功能获得或丧失，如衔接蛋白、酶、剪接体成分、细胞周期检查点调节剂、转录因子或细胞信号通路中的蛋白。在转录、翻译和翻译后修饰（如甲基化、去磷酸化或乙酰化）等各个水平的干扰都可能导致这些改变。ASXL1、EZH2、IDH1、IDH2、TET2、SRSF2、U2AF1、TP53、NRAS、KRAS、PTPN11、SH2B3/LNK 和 RUNX1 等突变基因在 MPN 中遗传物质表达、修饰和蛋白功能操纵的不同阶段发挥着积极作用。这些突变也与 MPN-BP 的进展相关，并可能促成其进展。在这篇综述中，我们总结了它们常见的突变谱、功能以及与 MPN-BP 进展的关系。
