在接受强化治疗的急性髓系白血病患者中，[基因名称]功能丧失突变是不良预后的独立标志物。 （你原文中“Loss-of-Function Mutations of ”后面缺少具体基因名称）
Loss-of-Function Mutations of Are an Independent Marker of Adverse Outcomes in Intensively Treated Patients with Acute Myeloid Leukemia.
作者信息
Eckardt Jan-Niklas, Stasik Sebastian, Kramer Michael, Röllig Christoph, Krämer Alwin, Scholl Sebastian, Hochhaus Andreas, Crysandt Martina, Brümmendorf Tim H, Naumann Ralph, Steffen Björn, Kunzmann Volker, Einsele Hermann, Schaich Markus, Burchert Andreas, Neubauer Andreas, Schäfer-Eckart Kerstin, Schliemann Christoph, Krause Stefan W, Herbst Regina, Hänel Mathias, Frickhofen Norbert, Noppeney Richard, Kaiser Ulrich, Baldus Claudia D, Kaufmann Martin, Rácil Zdenek, Platzbecker Uwe, Berdel Wolfgang E, Mayer Jiří, Serve Hubert, Müller-Tidow Carsten, Ehninger Gerhard, Stölzel Friedrich, Kroschinsky Frank, Schetelig Johannes, Bornhäuser Martin, Thiede Christian, Middeke Jan Moritz
机构信息
Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus, 01307 Dresden, Germany.
Deutsches Krebsforschungszentrum (DKFZ) and Medizinische Klinik V, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany.
出版信息
Cancers (Basel). 2021 Apr 26;13(9):2095. doi: 10.3390/cancers13092095.
Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The corepressor and its homolog, the , have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. and mutations were found in 71 (4.6%) and 53 patients (3.5%), respectively. Frequently co-mutated genes were , and . Mutated and loss-of-function mutations of were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of had a significantly reduced median event-free survival (HR = 1.464 (95%-Confidence Interval (CI): 1.005-2.134), = 0.047), relapse-free survival (HR = 1.904 (95%-CI: 1.163-3.117), = 0.01), and trend for reduced overall survival (HR = 1.495 (95%-CI: 0.990-2.258), = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of regarding risk stratification in AML, which may influence treatment allocation.
急性髓系白血病（AML）的特征是存在复发性基因事件。共抑制因子及其同源物已被报道在AML中是罕见但复发性的突变。此前，规模较小的研究报告了关于其对预后影响的相互矛盾的结果。在此，我们回顾性分析了1529例新诊断并接受强化治疗的AML患者的大型队列。分别在71例（4.6%）和53例患者（3.5%）中发现了和突变。常见的共突变基因有、和。在ELN2017中危组中，突变和功能缺失突变明显更为常见。携带功能缺失突变的患者在多变量分析中，无事件生存期（HR = 1.464（95%置信区间（CI）：1.005 - 2.134），= 0.047）、无复发生存期（HR = 1.904（95%CI：1.163 - 3.117），= 0.01）显著降低，总生存期有降低趋势（HR = 1.495（95%CI：0.990 - 2.258），= 0.056）。我们的研究确立了功能缺失突变在AML风险分层中的新作用，这可能会影响治疗分配。
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