文章：

新型复发性细胞遗传学异常预测四倍体/近四倍体骨髓增生异常综合征与急性髓系白血病患者总体生存率

Novel Recurrent Cytogenetic Abnormalities Predict Overall Survival in Tetraploid/Near-Tetraploid Myelodysplastic Syndrome and Acute Myeloid Leukemia

原文发布日期：10 April 2025

DOI: 10.3390/cancers17081277

类型: Article

开放获取: 是

英文摘要：

Background/Objectives: Tetraploidy (4n = 92 chromosomes) and near-tetraploidy (81–103 chromosomes) (T/NT) are uncommon cytogenetic events in MDS/AML (~1%). Abnormalities reported to be associated with T/NT MDS/AML include −5/del(5q), −7/del(7q), +8, and +21. However, other clinically relevant abnormalities likely remain “hidden” in long strings of ISCN cytogenetic nomenclature when evaluated visually. To date, no studies have had the statistical power and a computational method to identify novel recurrent abnormalities associated with the T/NT karyotype or overall survival (OS). Methods: Using CytoGPS, a bioinformatic tool we developed, we converted karyotypes from a combined cohort of 75 T/NT MDS/AML cases from two institutions into a binary Loss–Gain–Fusion model, which is analyzable using computational methods. Results: On univariate analyses, age as a continuous variable (p= 0.032), prior treatment (p= 0.011), and cohort (p= 0.025) were associated with OS; age ≥ 60 years (p= 0.316), gender (p= 0.916), karyotypic complexity (p= 0.175), time from diagnosis to T/NT karyotype identification (p= 0.419), and clone size (p= 0.316) had no effect. Univariate analyses of karyotypes demonstrated that −5, −16, −18, del(11)(p15.1p15.4), del(13)(q12.11q22.3), and +8 were associated with poorer OS (unadjustedp< 0.05). Conclusions: Using the results of univariate analyses to build multivariate models of OS, the best predictor of OS was the presence of any one of these six cytogenetic abnormalities.

摘要翻译： 

背景/目的：四倍体（4n = 92条染色体）和近四倍体（81–103条染色体）是骨髓增生异常综合征/急性髓系白血病中较为罕见的细胞遗传学事件（约占1%）。据报道，与四倍体/近四倍体骨髓增生异常综合征/急性髓系白血病相关的异常包括-5/del(5q)、-7/del(7q)、+8和+21。然而，在通过视觉评估国际人类细胞遗传学命名体系的长串命名时，其他具有临床意义的异常可能仍被“隐藏”。迄今为止，尚无研究具备足够的统计效能和计算方法来识别与四倍体/近四倍体核型或总生存期相关的新型复发性异常。方法：利用我们开发的生物信息学工具CytoGPS，将来自两个机构的75例四倍体/近四倍体骨髓增生异常综合征/急性髓系白血病病例的核型转换为可进行计算的二元“缺失-获得-融合”模型。结果：单变量分析显示，年龄作为连续变量、既往治疗史以及队列来源与总生存期相关；而年龄≥60岁、性别、核型复杂性、从诊断到四倍体/近四倍体核型识别的时间以及克隆大小则无显著影响。对核型的单变量分析表明，-5、-16、-18、del(11)(p15.1p15.4)、del(13)(q12.11q22.3)和+8与较差的总生存期相关。结论：利用单变量分析结果构建总生存期的多变量模型，最佳的总生存期预测因子是这六种细胞遗传学异常中任何一种的存在。

原文链接：

Novel Recurrent Cytogenetic Abnormalities Predict Overall Survival in Tetraploid/Near-Tetraploid Myelodysplastic Syndrome and Acute Myeloid Leukemia