Genomic characterisation of Chinese myeloid malignancies and its clinical correlates: insights from targeted next-generation sequencing

Purposes Gene mutations identified through next-generation sequencing (NGS) have been increasingly recognised for their clinical significance in myeloid malignancies. However, data concerning Chinese populations remain limited. This study aimed to characterise mutation profiles in Chinese patients with myeloid malignancies and to evaluate the associations of genetic alterations with clinical features, disease progression, and prognosis. Methods Targeted sequencing using a 110-gene panel was performed on 184 samples derived from 174 patients diagnosed with acute myeloid leukaemia (AML, n = 108), myelodysplastic syndromes (MDS, n = 66), and chronic myelomonocytic leukaemia (CMML, n = 10). Prognostic relevance of clinical variables, gene mutations, and single nucleotide polymorphisms (SNPs) was assessed using univariate and multivariate Cox regression analyses. Results In newly diagnosed AML cases, the most frequently mutated genes included FLT3 (19%), NPM1 (19%), DNMT3A (17%), and NRAS (17%). In MDS, mutations in DNMT3A (21%), TP53 (21%), and TET2 (19%) were most prevalent. Among CMML patients, ASXL1 and SRSF2 mutations were observed in 50%, and RUNX1 in 40% of cases. A significantly higher incidence of WT1 mutations was observed in relapsed AML compared with newly diagnosed cases. In patients with secondary AML transformed from CMML, NPM1 and FAT1 mutations occurred at significantly higher frequencies than in CMML alone. Specific SNPs in FAT1 , PDGFRA , SETBP1 , and KMT2C were associated with poorer prognosis in AML. In MDS, TP53 mutations, FAT1 / IL7R SNPs, and elevated peripheral blood blast percentages were identified as adverse prognostic indicators. Conclusion Targeted NGS revealed distinct mutational landscapes in Chinese patients with AML, MDS, and CMML. These findings demonstrated associations between genetic alterations and clinical features, disease progression, and prognosis in Chinese patients with myeloid malignancies. However, the prognostic associations should be interpreted cautiously, as none of the evaluated variables remained independent prognostic factors in multivariate models.