Huang Xinhui, Li Xiao, Liu Qi, Guo Juan, Chen Jianan, Zhou Liyu, Song Luxi, Zhang Zheng, Su Jiying, Zhang Yumei, Yan Meng, He Qi, Wu Dong, Xu Feng, Chang Chunkang, Wu Lingyun
Department of Hematology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, China.
Department of Hematology, Shanghai Eighth People's Hospital, Shanghai, 200233, China.
Clin Exp Med. 2025 Jun 13;25(1):202. doi: 10.1007/s10238-025-01742-8.
The 20q deletion (del(20q)) is a recurrent chromosomal abnormality in individuals with myelodysplastic syndrome (MDS) and is associated with favourable outcomes when isolated. This study aims to analyse the clinical features and prognostic impact of del(20q) based on cytogenetic and molecular alterations. Among 1,527 patients with MDS, 101 (6.6%) exhibited del(20q): 67 (66.3%) had isolated del(20q), 16 (15.8%) had one additional chromosome abnormality (ACA), and 18 (17.8%) had ≥ 2 additional chromosome abnormalities (ACAs). Patients with ≥ 2 ACAs experienced shorter overall survival (OS) (12 months vs. 35 months vs. 24 months, respectively, p = 0.046) and leukaemia-free survival (LFS) (NR vs. NR vs. 22 months, respectively, p = 0.030), than those with one ACA or isolated del(20q). The del(20q) with ACAs subgroup had a higher incidence of ≥ 2 mutations and a greater median number of molecular mutations (p = 0.049 and p = 0.047, respectively). Interestingly, we found that multiple mutations within the same gene were present in 8.7% (6/69) of the analyzed samples. Notably, TET2 was the most frequently observed gene with multiple mutations, constituting 66.7% (4/6) of all cases. Furthermore, samples with TET2 mutations exhibited a significantly higher median number of mutations compared to those without TET2 mutations (3.0 [Interquartile Range [IQR], 1, 4] vs. 1.0[0, 2], p = 0.003). Patients with ≥ 2 mutations showed poorer OS and LFS (p < 0.001 and p = 0.007, respectively) compared to those with fewer mutations. The presence of multiple mutations (hazard ratio [HR] = 2.777, p = 0.049), U2AF1 mutations (HR = 3.595, p = 0.010), TET2 mutations (HR = 7.178, p = 0.002), and bone marrow blasts ≥ 10% (HR = 5.727, p = 0.002) were independently associated with poorer OS. In summary, del(20q) with ACAs is associated with more molecular abnormalities, increased risk of acute myeloid leukaemia transformation, and shorter OS than isolated del(20q). U2AF1 and TET2 mutations predict poor prognosis in patients with del(20q) MDS.
20号染色体缺失（del(20q)）是骨髓增生异常综合征（MDS）患者中常见的染色体异常，单独出现时与较好的预后相关。本研究旨在基于细胞遗传学和分子改变分析del(20q)的临床特征及预后影响。在1527例MDS患者中，101例（6.6%）出现del(20q)：67例（66.3%）为孤立性del(20q)，16例（15.8%）有一项额外染色体异常（ACA），18例（17.8%）有两项及以上额外染色体异常（ACA）。与有一项ACA或孤立性del(20q)的患者相比，有两项及以上ACA的患者总生存期（OS）（分别为12个月、35个月和24个月，p = 0.046）和无白血病生存期（LFS）（分别为未达到、未达到和22个月，p = 0.030）更短。伴有ACA的del(20q)亚组中，两项及以上突变的发生率更高，分子突变中位数更多（分别为p = 0.049和p = 0.047）。有趣的是，我们发现8.7%（6/69）的分析样本中同一基因存在多个突变。值得注意的是，TET2是最常观察到有多个突变的基因，占所有病例的66.7%（4/6）。此外，与无TET2突变的样本相比，有TET2突变的样本突变中位数显著更高（3.0 [四分位间距[IQR]，1, 4] 对 1.0[0, 2]，p = 0.003）。与突变较少的患者相比，有两项及以上突变的患者OS和LFS更差（分别为p < 0.001和p = 0.007）。多个突变的存在（风险比[HR] = 2.777，p = 0.049）、U2AF1突变（HR = 3.595，p = 0.010）、TET2突变（HR = 7.178，p = 0.002）以及骨髓原始细胞≥10%（HR = 5.727，p = 0.002）与较差的OS独立相关。总之，伴有ACA的del(20q)与更多分子异常有关，急性髓系白血病转化风险增加，且与孤立性del(20q)相比OS更短。U2AF1和TET2突变预示着del(20q) MDS患者预后不良。
