Monitoring of residual disease by next-generation deep-sequencing of RUNX1 mutations can identify acute myeloid leukemia patients with resistant disease
Monitoring of residual disease by next-generation deep-sequencing of RUNX1 mutations can identify acute myeloid leukemia patients with resistant disease
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DOI：
10.1038/leu.2013.239
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发表时间：
2014-01-01
期刊：
影响因子：
11.4
通讯作者：
Haferlach, T.
中科院分区：
文献类型：
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作者：
Kohlmann, A.;Nadarajah, N.;Haferlach, T.
我们研究了RUNX1(矮小相关转录因子1)突变的实用性和临床相关性，以及它们作为残留病检测标记物的应用。对814例急性髓系白血病患者进行了前瞻性突变筛查。确诊时，211/814(25.9%)患者携带突变，中位克隆大小为39%(范围：2-96%)。此外，对57名患者的诊断和复发配对样本进行了分析。在47/57(82.5%)病例中，在诊断时发现的相同改变在复发时存在，而在1/57(1.8%)病例中，来自诊断样本的突变不再被检测到。在9/57(15.8%)的病例中观察到差异，还包括新的RUNX1突变的出现，这些突变并不局限于诊断时受影响的区域。此外，在103名患者中，研究了完全缓解期间RUNX1突变残留水平对预后的影响。根据残存突变负荷的中位数将患者分为好应答者和差应答者(中位数：3.61%；范围：0.03-48.0%)，两者无事件的差异有统计学意义(中位数21.0个月对5.7个月，P
We studied the utility and clinical relevance of RUNX1 (runt-related transcription factor 1) mutations and their application as residual disease detection markers using next-generation deep-sequencing. Mutation screening was prospectively performed in 814 acute myeloid leukemia patients. At diagnosis, 211/814 (25.9%) patients harbored mutations with a median clone size of 39% (range: 2-96%). Furthermore, in 57 patients paired samples from diagnosis and relapse were analyzed. In 47/57 (82.5%) cases the same alterations detected at diagnosis were present at relapse, whereas in 1/57 (1.8%) cases the mutation from the diagnostic sample was no longer detectable. Discrepancies were observed in 9/57 (15.8%) cases, also including the occurrence of novel RUNX1 mutations not restricted to those regions affected at diagnosis. Moreover, in 103 patients the prognostic impact of residual levels of RUNX1 mutations during complete remission was studied. Separation of patients according to median residual mutation burden into 'good responders' and 'poor responders' (median: 3.61%; range: 0.03-48.0%) resulted in significant differences of both event-free (median 21.0 vs 5.7 months, P