Myeloid neoplasms represent a broad spectrum of hematological disorders for which somatic mutation status in key driver genes is important for diagnosis, prognosis and treatment. Here we summarize the findings of a targeted, next generation sequencing laboratory developed test in 24,639 clinical myeloid samples. Data were analyzed comprehensively and as part of individual cohorts specific to acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and myeloproliferative neoplasms (MPN). Overall, 48,015 variants were detected, and variants were found in all 50 genes in the panel. The mean number of mutations per patient was 1.95. Mutation number increased with age (Spearman's rank correlation coefficient, ρ = 0.29, P < 0.0001) and was higher in patients with AML than MDS or MPN (Student's t-test, P < 0.0001). TET2 was the most common mutation detected (19.1% of samples; 4,695/24,639) including 7.7% (1,908/24,639) with multi-hit TET2 mutations. Mutation frequency was correlated between patients with cytopenias and MDS (Spearman's, ρ = 0.97, P < 2.2×10^–16) with the MDS diagnostic gene SF3B1 being the only notable outlier. This large retrospective study shows the utility of NGS testing to inform clinical decisions during routine clinical care and highlights the mutational landscape of a broad population of myeloid patients.

骨髓肿瘤代表了广泛的血液疾病，关键驱动基因的体细胞突变状态对于诊断、预后和治疗非常重要。在这里，我们总结了针对 24,639 份临床骨髓样本的下一代靶向测序实验室开发的测试结果。对数据进行了全面分析，并将其作为针对急性髓系白血病（AML）、骨髓增生异常综合征（MDS）和骨髓增生性肿瘤（MPN）的个体队列的一部分。总体而言，检测到了 48,015 个变异，并且在面板中的所有 50 个基因中都发现了变异。每个患者的平均突变数为 1.95。突变数量随着年龄的增长而增加（Spearman 等级相关系数，ρ = 0.29，P <  0.0001），并且 AML 患者的突变数量高于 MDS 或 MPN（学生t检验，P <  0.0001）。TET2是检测到的最常见突变（19.1% 的样本；4,695/24,639），其中 7.7%（1,908/24,639）存在多次TET2突变。血细胞减少症和 MDS 患者之间的突变频率相关（Spearman's，ρ = 0.97，P <  2.2×10 ^–16），MDS 诊断基因SF3B1是唯一显着的异常值。这项大型回顾性研究展示了 NGS 检测在常规临床护理期间为临床决策提供信息的实用性，并强调了广大骨髓患者群体的突变情况。