Gene Mutation Spectrum of Patients with Myelodysplastic Syndrome and Progression to Acute Myeloid Leukemia

Aim: This study aimed to investigate the regularity of gene mutations in patients with myelodysplastic syndrome (MDS) and in those that progressed to acute myeloid leukemia (MDS/AML). Patients & methods: High-throughput sequencing technology was used to detect gene mutations in 99 newly diagnosed patients with MDS or MDS/AML. Results: Gene mutations were detected in 88 patients. The mutation incidence in the MDS/AML group was significantly higher than that in the MDS group. Statistically significant differences were observed between the MDS with refractory anemia (MDS-RA) and MDS-RA with excess blasts groups and between the MDS/AML and MDS-RA groups. Conclusion: Our data demonstrate that there is a cumulative accumulation of gene mutations, especially in transcription factor genes, during disease progression in MDS and MDS/AML.Lay abstract This study investigated the regularity of gene mutations in patients with myelodysplastic syndrome (MDS) and in those that have progressed to acute myeloid leukemia (MDS/AML). High-throughput sequencing was used to detect mutations in 58 genes with known clinical significance in 99 patients who were newly diagnosed with MDS or MDS/AML. A total of 28 mutated genes and 214 mutations were detected in 88 (88.9%) patients. The most frequently mutated gene was U2AF1 (13.55%; 29/214), followed by ASXL1 (10.28%; 22/214), TP53 (7.09%; 15/214), and RUNX1 (7.09%; 15/214). The mutation rate in the MDS/AML group was significantly higher than in the MDS group (100 vs 84.51%; p = 0.031). The average number of mutations per patient was 1.40, 2.20 and 2.64 in the MDS-refractory anemia (RA), MDS-RA with excess blast (RAEB) and MDS/AML groups, respectively. Statistically significant differences were observed between the MDS-RA and MDS-RAEB groups (p = 0.031) and between the MDS/AML and MDS-RA groups (p = 0.003). Signal transduction gene mutations were more frequent in the MDS/AML than in the MDS group (50% vs 22.54%; p = 0.014), especially in the FLT3 (14.29% vs 0; p = 0.005) and PTPN11 (17.86 vs 2.82%; p = 0.018) genes. Statistically significant (p < 0.05) correlations were found in 12 mutated gene combinations. TP53 mutations were mutually exclusive with RNA splicing factor gene mutations (p = 0.001). U2AF1 S34 mutations were associated with trisomy 8 (22.22 vs 5.97%; p = 0.03), and TP53 mutations were associated with complex karyotypes. Our data demonstrate that there is cumulative accumulation of gene mutations, especially in transcription factor genes, during disease progression in MDS and MDS/AML. The data also indicate there are synergistic pathogenicity and mutually exclusive effects among gene mutations and chromosomal abnormalities.