Wang Kai, Zhou Feng, Cai Xiaohui, Chao Hongying, Zhang Ri, Chen Suning
Department of Hematology, The First Affiliated Hospital of Suzhou University, Jiangsu Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of Ministry of Health, Suzhou, People's Republic of China.
Department of Hematology, Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou, People's Republic of China.
Hematology. 2020 Dec;25(1):211-218. doi: 10.1080/16078454.2020.1765561.
RUNX1 mutations in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) are associated with distinct clinicopathologic features. However, the clinical and laboratory characteristics of the myeloid malignancies may be influenced by the presence of more concomitant mutations. The aim of this study is to provide a further understanding of mutational landscape in the context of RUNX1 mutation in AML/MDS. The present study screened for 49 mutations using next-generation sequencing (NGS). -, and mutations were detected by PCR Sanger sequencing. One or more co-mutations were detected in all AML and 92.3% MDS patients in the context of RUNX1 mutation. The most common co-mutation was DNMT3A, followed by NRAS, IDH1, and FLT3-ITD in AML. The four more frequently co-mutated genes were U2AF1, TET2, PTPN11, and ASXL1 in MDS. We also identified a significantly difference in co-mutational spectrums between RUNX1-mutatedAML and MDS patients, as reflected in incidence of DNMT3A (35.1% 7.7%), FLT3-ITD (16.2% 0%) and U2AF1 (10.8% 30.7%) mutations. RUNX1-mutated AML patients with 3, or ≥4 co-mutations showed much lower CR rate than that with 2 additional mutations (= 0.0247, 0.00919). RUNX1-mutated AML and MDS are associated with a different complex co-mutation cluster. Some co-mutations have certain influence on the clinical feature and CR rate in the context of RUNX1 mutation.
急性髓系白血病（AML）和骨髓增生异常综合征（MDS）中的RUNX1突变与不同的临床病理特征相关。然而，髓系恶性肿瘤的临床和实验室特征可能会受到更多伴随突变的影响。本研究的目的是进一步了解AML/MDS中RUNX1突变背景下的突变图谱。本研究使用下一代测序（NGS）筛选了49种突变。通过PCR Sanger测序检测到 -、 和 突变。在RUNX1突变背景下，所有AML患者和92.3%的MDS患者中检测到一个或多个共突变。AML中最常见的共突变是DNMT3A，其次是NRAS、IDH1和FLT3-ITD。MDS中另外四个更频繁共突变的基因是U2AF1、TET2、PTPN11和ASXL1。我们还发现RUNX1突变的AML和MDS患者之间的共突变谱存在显著差异，如DNMT3A（35.1% 7.7%）、FLT3-ITD（16.2% 0%）和U2AF1（10.8% 30.7%）突变的发生率所示。具有3个或≥4个共突变的RUNX1突变AML患者的完全缓解率远低于具有2个额外突变的患者（= 0.0247，0.00919）。RUNX突变的AML和MDS与不同的复杂共突变簇相关。在RUNX1突变背景下，一些共突变对临床特征和完全缓解率有一定影响。
