Hematology Department, İzmir City Hospital, Bayrakli/İzmir, Turkey.
Genetic Diagnosis Center, İzmir City Hospital, Bayrakli/İzmir, Turkey.
Medicine (Baltimore). 2024 Oct 11;103(41):e39909. doi: 10.1097/MD.0000000000039909.
Myelodysplastic syndromes (MDS) are clinically heterogeneous disorders characterized by peripheral blood cytopenias, poor differentiation, clonal hematopoiesis, and increased risk of developing acute myeloid leukemia (AML). While somatic mutations do not currently feature in prognostic scoring systems, they may impact the clinical phenotype. In recent years, next-generation sequencing (NGS) has enabled the opportunity to identify an increasing number of genetic abnormalities, including recurrent modifications in the TP53, DNMT3A, NRAS, NPM1, RUNX1, and FLT3 genes. Bone marrow aspirate samples of 56 patients with MDS were investigated for mutations using NGS. We compared the relationship between gene mutation status and laboratory characteristics, such as certain cytopenias, the revised international prognostic scoring system, MDS subtypes, karyotypes, AML development, and overall survival. Twenty-one genes were found to have gene mutations, including ASXL1, TET2, SRSF2, EZH2, CSF3R, NRAS, ETV6, SETBP1, RUNX1, DDX41, U2AF1, JAK2, FLT3ITD, SF3B1, DNAMT3A, PHF6, TP53, CEBPA, CBL, IDH2, and GATA2. At least one point mutation occurred in 64.2% of all patients, including 58.3% of those with normal cytogenetics. Thrombocytopenia (P = .016), anemia (P = .018), decreased overall survival (P = .017), and increased AML transformation (P = .023) have been revealed to be linked to non-SF3B1 mutations. MDS are frequently associated with somatic point mutations. According to early findings, NGS panels are extremely effective instruments that provide an entirely new viewpoint on the disease for particular individuals. Future prognostications will depend more on NGS because those who exhibit normal cytogenetics may additionally have gene mutations.
骨髓增生异常综合征(MDS)是一组临床表现异质性的疾病,其特征为外周血细胞减少、分化不良、克隆性造血以及急性髓系白血病(AML)风险增加。尽管体细胞突变目前未被纳入预后评分系统,但它们可能会影响临床表型。近年来,下一代测序(NGS)技术使我们有机会发现越来越多的遗传异常,包括 TP53、DNMT3A、NRAS、NPM1、RUNX1 和 FLT3 等基因的反复突变。对 56 例 MDS 患者的骨髓抽吸物样本进行 NGS 检测以发现基因突变。我们比较了基因突变状态与实验室特征(如某些血细胞减少、修订后的国际预后评分系统、MDS 亚型、核型、AML 发展和总生存)之间的关系。发现 21 个基因存在基因突变,包括 ASXL1、TET2、SRSF2、EZH2、CSF3R、NRAS、ETV6、SETBP1、RUNX1、DDX41、U2AF1、JAK2、FLT3 ITD、SF3B1、DNMT3A、PHF6、TP53、CEBPA、CBL、IDH2 和 GATA2。所有患者中至少有一个点突变,包括 58.3%的核型正常患者。血小板减少症(P=0.016)、贫血(P=0.018)、总生存时间缩短(P=0.017)和 AML 转化率增加(P=0.023)与非 SF3B1 突变相关。MDS 常与体细胞点突变相关。根据初步发现,NGS 面板是一种非常有效的工具,可为特定个体提供对疾病的全新视角。未来的预后将更多地依赖于 NGS,因为那些核型正常的患者可能还存在基因突变。