Department of Hematology, Xuanwu Hospital, Capital Medical University, Beijing, People's Republic of China.
Hematology. 2024 Dec;29(1):2387878. doi: 10.1080/16078454.2024.2387878. Epub 2024 Aug 14.
MDS and AML characterized by variations have a poor prognosis in general. However, specifically, differences in prognosis have also been observed in patients with different variants and VAFs. Here, we retrospectively analyzed datasets of patients with MDS, MPN, and AML who underwent targeted DNA sequencing from February 2018 to December 2023, and patients with reportable variations were screened. Demographic data and clinical data were collected, and the relationship between alterations and patient prognosis (AML/MDS) was analyzed using the cBioPortal and Kaplan-Meier Plotter databases. The relationship between the VAFs of variations and prognoses was analyzed using data from the present study. Sixty-two variants of were identified in 58 patients. We mainly identified single mutations (79.31%, 46/58), followed by double (17.24%, 10/58) and triple (3.45%, 2/58) mutations. The variations were mainly enriched in exon4-exon8 of . Missense (72.58%, 45/62) mutations were the main type of variations, followed by splice-site (9.68%, 6/62), nonsense (9.68%, 6/62), frameshift (6.45%, 4/62), and indel (1.61%, 1/62) mutations. In this study, p.Arg175His and p.Arg273His were high-frequency mutations, and and were commonly co-mutated genes in the three types of myeloid neoplasms; However, we reported some new variants in MPN that have not been found in the public database. Moreover, MDS or AML characterized by altered had a shorter OS than patients in the unaltered group (<0.01), low mRNA levels were associated with shorter OS in patients with AML (<0.01). Data from our center further found higher VAF (≥10%) associated with shorter OS in patients with MDS (median 2.75 vs. 24 months) (<0.01). mutations are mainly enriched in exon4-exon8, are missense and single mutations in myeloid neoplasms, and are associated with poor prognosis of MDS/AML, and higher VAF (≥10%) of mutations associated with a shorter OS in patients with MDS.
MDS 和 AML 伴有变异一般预后较差。然而，具体而言，不同变异和 VAF 的患者预后也存在差异。在这里，我们回顾性分析了 2018 年 2 月至 2023 年 12 月接受靶向 DNA 测序的 MDS、MPN 和 AML 患者的数据集，并筛选出有报告意义的变异患者。收集患者的人口统计学和临床数据，并使用 cBioPortal 和 Kaplan-Meier Plotter 数据库分析变异与患者预后（AML/MDS）的关系。使用本研究的数据分析变异的 VAF 与预后的关系。在 58 例患者中确定了 62 个 变异。我们主要发现了单突变（79.31%，46/58），其次是双突变（17.24%，10/58）和三突变（3.45%，2/58）。变异主要富集在 的外显子 4-8。错义（72.58%，45/62）突变是变异的主要类型，其次是剪接位点（9.68%，6/62）、无义（9.68%，6/62）、移码（6.45%，4/62）和插入缺失（1.61%，1/62）突变。在本研究中，p.Arg175His 和 p.Arg273His 是高频 突变，和 是三种骨髓增生性肿瘤中常见的共突变基因；然而，我们报告了一些在 MPN 中发现的新的 变异，这些变异在公共数据库中尚未发现。此外，改变的 特征的 MDS 或 AML 患者的 OS 短于未改变组（<0.01），AML 患者中较低的 mRNA 水平与较短的 OS 相关（<0.01）。来自我们中心的数据进一步发现，MDS 患者中更高的 VAF（≥10%）与较短的 OS 相关（中位 2.75 与 24 个月）（<0.01）。 突变主要富集在外显子 4-8，在骨髓增生性肿瘤中为错义且单突变，与 MDS/AML 的不良预后相关，较高的 VAF（≥10%）与 MDS 患者较短的 OS 相关。
