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Abstract：
The prognostic impact of biallelic ATM abnormalities (ATM mutation and concurrent 11q deletion) remains unknown. We studied ATM, BIRC3, SF3B1, and NOTCH1 genes in 118 treatment-naïve CLL patients at diagnosis. Patients with biallelic ATM alteration had a similar time to first treatment (TTFT) and shorter overall survival (OS) compared with patients with isolated 11q deletion and shorter TTFT and OS when compared to patients with wild-type ATM. Furthermore, biallelic ATM alteration (HR: 6.4; p ≤ 0.007) was significantly associated with an increased risk of death similar to p53 deletion (HR: 6.1; p ≤ 0.004), superior to 11q deletion alone (HR: 2.8; p ≤ 0.022) and independent of other significant parameters such as age, advanced clinical stage, and complex karyotype. Our results suggest the identification of ATM mutations in CLL patients with 11q deletion at diagnosis is clinically relevant and predicts disease progression, poor response to the treatment, and reduced OS independent of other molecular prognostic factors.
摘要：
双等位基因ATM异常（ATM突变和并发11q缺失）的预后影响仍然未知。我们研究过ATM,118例初治CLL患者诊断时的BIRC3、SF3B1和NOTCH1基因。与具有野生型ATM的患者相比，具有双等位基因ATM改变的患者与首次治疗（TTFT）的时间相似，与具有分离的11q缺失和较短的TTFT和OS的患者相比，总生存期（OS）更短。此外，双等位基因ATM改变(HR:6.4;p≤0.007)与p53缺失(HR:6.1;p≤0.004)相似的死亡风险增加显著相关,优于仅11q缺失（HR：2.8；p≤0.022），并且独立于其他重要参数，例如年龄，晚期临床阶段，和复杂的核型。我们的结果表明，在CLL患者中发现ATM突变与11q缺失在诊断时具有临床意义，并可预测疾病进展。对治疗反应不佳，和OS降低独立于其他分子预后因素。
