Gene mutation analysis using next-generation sequencing and its clinical significance in patients with myeloid neoplasm: A multi-center study from China

Cancer Med. 2023 Apr;12(8):9332-9350. doi: 10.1002/cam4.5690. Epub 2023 Feb 17.


Background: Myeloid neoplasms (MN) tend to relapse and deteriorate. Exploring the genomic mutation landscape of MN using next-generation sequencing (NGS) is a great measure to clarify the mechanism of oncogenesis and progression of MN.

Methods: This multicenter retrospective study investigated 303 patients with MN using NGS from 2019 to 2021. The characteristics of the mutation landscape in the MN subgroups and the clinical value of gene variants were analyzed.

Results: At least one mutation was detected in 88.11% of the patients (267/303). TET2 was the most common mutation in the cohort, followed by GATA2, ASXL1, FLT3, DNMT3A, and TP53. Among patients with myeloid leukemia (ML), multivariate analysis showed that patients aged ≥60 years had lower overall survival (OS, p = 0.004). Further analysis showed TET2, NPM1, SRSF2, and IDH1 gene mutations, and epigenetic genes (p < 0.050) presented significantly higher frequency in older patients. In patients with myelodysplastic syndrome (MDS) and myelodysplastic neoplasms (MPN), univariate analysis showed that BCORL1 had a significant impact on OS (p = 0.040); however, in multivariate analysis, there were no factors significantly associated with OS. Differential analysis of genetic mutations showed FLT3, TP53, MUC16, SRSF2, and KDM5A mutated more frequently (p < 0.050) in secondary acute myeloid leukemia (s-AML) than in MDS and MPN. TP53, U2AF1, SRSF2, and KDM5A were mutated more frequently (p < 0.050) in s-AML than in primary AML. KDM5A was observed to be restricted to patients with s-AML in this study, and only co-occurred with MUC16 and TP53 (2/2, 100%). Another mutation was MUC16, and its co-occurrence pattern differed between s-AML and AML. MUC16 mutations co-occurred with KDM5A and TP53 in 66.7% (2/3) of patients with s-AML and co-occurred with CEBPA in 100% (4/4) of patients with AML.

Conclusions: Our results demonstrate different genomic mutation patterns in the MN subgroups and highlight the clinical value of genetic variants.

Keywords: acute myeloid leukemia; gene mutation; myeloid neoplasm; next-generation sequencing.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • China / epidemiology
  • Clinical Relevance
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Leukemia, Myeloid, Acute* / genetics
  • Mutation
  • Myelodysplastic Syndromes* / genetics
  • Myeloproliferative Disorders*
  • Nucleophosmin
  • Prognosis
  • Retinoblastoma-Binding Protein 2 / genetics
  • Retrospective Studies


  • Nucleophosmin
  • KDM5A protein, human
  • Retinoblastoma-Binding Protein 2