Symes Emily O, Wang Peng, Sojitra Payal, Menon Madhu P, Patel Anand A, Hasan Faheema, Ghosh Sharmila, Roloff Gregory W, Zhou Qianghua, Findley Anthony, Badar Talha, Zhang Jingjing, Tariq Hamza, Chang Hong, Bell Robert C, Perry Anamarija M, Venkataraman Girish
Pathology (Hematopathology & Genomic Pathology), Medicine (Hematology/Oncology), The University of Chicago Medicine, Chicago, Illinois, USA.
Pathology, Robert Wood Johnson University Hospital, New Brunswick, New Jersey, USA.
Br J Haematol. 2025 Apr;206(4):1103-1108. doi: 10.1111/bjh.19895. Epub 2024 Nov 17.
To assess the relevance of co-occurring somatic mutations in TP53-mutated myeloid neoplasms with ≥10% blasts, we pooled 325 individuals from 10 centres. We focused on comparing three published somatic co-alteration signatures comprising (1) nine MDS-related genes ('ICC-MDSR'), (2) ICC-MDSR + additional secondary mutations-related genes ('Tazi signature') and (3) EPI6 (comprising six genes). Outcomes examined were 24-month overall survival (OS24) and front-line complete response (CR1). The median age was 69 years with 77% receiving front-line hypomethylating agents (HMA). All three signatures ICC-MDSR (p = 0.009), Tazi signature (p = 0.001) and EPI6 (p = 0.025) predicted inferior CR1. In the low-intensity (HMA) subgroup, only Tazi signature (p = 0.026) predicted inferior CR1. In OS24 analysis of the HMA-treated subgroup (N = 200), only Tazi signature was adverse (hazard ratio, HR = 1.6 [1.1-2.2]; p = 0.011). However, a forward stepwise multivariable age-adjusted Cox model including all three signatures picked EPI6 as the sole significant adverse predictor in the entire cohort (p = 0.0001) as well as within the HMA-treated subgroup (p = 0.0071). These data confirm the value of testing co-occurring somatic alterations even within a high-grade TP53-mutated myeloid neoplasm cohort.
为了评估伴有≥10%原始细胞的TP53突变型髓系肿瘤中同时发生的体细胞突变的相关性，我们汇总了来自10个中心的325名个体的数据。我们着重比较了三个已发表的体细胞共改变特征，包括：（1）9个与骨髓增生异常综合征（MDS）相关的基因（“ICC-MDSR”）；（2）ICC-MDSR加上其他继发突变相关基因（“Tazi特征”）；（3）EPI6（由6个基因组成）。所检测的结局指标为24个月总生存率（OS24）和一线完全缓解率（CR1）。中位年龄为69岁，77%的患者接受一线去甲基化药物（HMA）治疗。所有三个特征，即ICC-MDSR（p = 0.009）、Tazi特征（p = 0.001）和EPI6（p = 0.025）均预测CR1较差。在低强度（HMA）亚组中，只有Tazi特征（p = 0.026）预测CR1较差。在接受HMA治疗亚组（N = 200）的OS24分析中，只有Tazi特征具有不良影响（风险比，HR = 1.6 [1.1 - 2.2]；p = 0.011）。然而，一个纳入所有三个特征的向前逐步多变量年龄校正Cox模型显示，在整个队列（p = 0.0001）以及接受HMA治疗的亚组中（p = 0.0071），EPI6是唯一显著的不良预测因素。这些数据证实了即使在高级别TP53突变型髓系肿瘤队列中检测同时发生的体细胞改变的价值。
