中国复杂核型骨髓增生异常综合征患者的临床及分子特征分析

Analysis of clinical and molecular features of MDS patients with complex karyotype in China.

作者信息

Ren Yanling, Mei Chen, Ye Li, Luo Yingwan, Zhou Xinping, Yang Haiyang, Lin Peipei, Xu Weilai, Ma Liya, Jin Jie, Tong Hongyan

机构信息

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China; Myelodysplastic Syndromes Diagnosis and Therapy Center, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China.

Department of Hematology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang, China.

出版信息

Blood Cells Mol Dis. 2019 Mar;75:13-19. doi: 10.1016/j.bcmd.2018.11.006. Epub 2018 Nov 22.

DOI:10.1016/j.bcmd.2018.11.006

PMID:30530101

Abstract

We retrospectively analyzed 101 primary MDS patients with complex karyotype during January 2010 and April 2017.The median overall survival (OS) time was 13 (95% CI 9.98-16.02) months, and there was no significant difference in OS for different treatment. Chromosome 5/7 involvement was common (78.22%, 79/101) and associated with shorter OS (12 months vs. 28 months, P < 0.01) Monosomal karyotype (MK) is overlapped with CK in 79 patients, but was not statistically associated with shorter OS. While in 59 cases with genes sequenced, 57 (96.61%) patients were found to have at least one mutation of known significance, and TP53 was the most frequent (74.58%, 44/59), the median OS of patients with TP53 mutation was shorter than those without (10 vs. 27 months, P < 0.01). Multivariate analysis demonstrated that only TP53 mutation was the strongest independent prognostic factor for OS. Moreover, high variant allele frequency (VAF) of TP53 mutation (median VAF was 70.00%) was seen and associated with adverse survival (9 months vs. 13 months, p = 0.04). In conclusion, MDS patients with CK implied an unfavorable outcome regardless of any treatment, TP53 mutation occurs at a high frequency and has a higher VAF, both were associated with worse survival.

摘要

我们回顾性分析了2010年1月至2017年4月期间101例具有复杂核型的原发性骨髓增生异常综合征（MDS）患者。中位总生存期（OS）为13个月（95%置信区间9.98 - 16.02），不同治疗方式的OS无显著差异。5号/7号染色体受累常见（78.22%，79/101），且与较短的OS相关（12个月 vs. 28个月，P < 0.01）。79例患者中，单倍体核型（MK）与复杂核型（CK）重叠，但与较短的OS无统计学关联。在59例进行基因测序的病例中，57例（96.61%）患者被发现至少有一个具有已知意义的突变，TP53是最常见的突变基因（74.58%，44/59），TP53突变患者的中位OS短于未突变患者（10个月 vs. 27个月，P < 0.01）。多因素分析表明，只有TP53突变是OS最强的独立预后因素。此外，观察到TP53突变的高变异等位基因频率（VAF）（中位VAF为70.00%），且与不良生存相关（9个月 vs. 13个月，p = 0.04）。总之，无论采用何种治疗，具有CK的MDS患者预后不良，TP53突变发生率高且VAF较高，两者均与较差的生存相关。