• Xiaohui Cai, Kai Wang, Feng Zhou, Hongying Chao, Ri Zhang, and Suning Chen.
• 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.
• Hematology. 2020 Dec 1; 25 (1): 211-218.

AbstractIntroduction: 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.Methods: The present study screened for 49 mutations using next-generation sequencing (NGS). FLT3-ITD, NPM1, and CEBPA mutations were detected by PCR Sanger sequencing.Results: 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% vs 7.7%), FLT3-ITD (16.2% vs 0%) and U2AF1 (10.8% vs 30.7%) mutations. RUNX1-mutated AML patients with 3, or ≥4 co-mutations showed much lower CR rate than that with 2 additional mutations (p = 0.0247, 0.00919).Conclusion: 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.

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