National Research Center for Hematology, Novy Zykovski lane 4a, 125167 Moscow, Russia.
Genes (Basel). 2021 Apr 12;12(4):559. doi: 10.3390/genes12040559.
(Janus kinase 2) V617F, (Calreticulin) exon 9, and (receptor for thrombopoietin) exon 10 mutations are associated with the vast majority of Ph-negative chronic myeloproliferative neoplasms (MPNs). These mutations affect sequential stages of proliferative signal transduction and therefore, after the emergence of one type of mutation, other types should not have any selective advantages for clonal expansion. However, simultaneous findings of these mutations have been reported by different investigators in up to 10% of MPN cases. Our study includes DNA samples from 1958 patients with clinical evidence of MPN, admitted to the National Research Center for Hematology for genetic analysis between 2016 and 2019. In 315 of 1402 cases (22.6%), mutations were detected. In 23 of these 315 cases (7.3%), the JAK2 V617F mutation was found in addition to the mutation. In 16 from 24 (69.6%) cases, with combined and mutations, V617F allele burden was lower than 1%. A combination of V617F with W515L/K was also observed in 1 out of 1348 cases, only. allele burden in this case was also lower than 1%. Additional mutations may coexist over the low background of JAK2 V617F allele. Therefore, in cases of detecting MPNs with a low allelic load V617F, it may be advisable to search for other molecular markers, primarily mutations in exon 9 of . The load of the combined mutations measured at different time points may indicate that, at least in some cases, these mutations could be represented by different clones of malignant cells.
(Janus kinase 2)V617F、(钙网蛋白)exon 9 和(血小板生成素受体)exon 10 突变与绝大多数 Ph 阴性慢性骨髓增殖性肿瘤(MPN)相关。这些突变影响增殖信号转导的连续阶段,因此,在出现一种突变类型后,其他类型的突变不应对克隆扩张具有任何选择优势。然而,不同的研究者已经在高达 10%的 MPN 病例中同时发现了这些突变。我们的研究包括了 1958 名有 MPN 临床证据的患者的 DNA 样本,这些样本于 2016 年至 2019 年在国家血液学研究中心进行了基因分析。在 1402 例病例中的 315 例(22.6%)中检测到突变。在这 315 例病例中的 23 例(7.3%)中,除了 突变外,还发现了 JAK2 V617F 突变。在 16 例合并 和 突变的病例中,V617F 等位基因负担低于 1%。在 1348 例病例中,仅观察到 1 例 V617F 与 W515L/K 的组合,该病例的 等位基因负担也低于 1%。额外的突变可能在 JAK2 V617F 等位基因的低背景下共存。因此,在检测到低等位基因负荷 V617F 的 MPN 时,可能需要寻找其他分子标记,主要是 exon 9 的突变。在不同时间点测量的合并突变的负荷可能表明,至少在某些情况下,这些突变可能由恶性细胞的不同克隆代表。
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