Patients with myelodysplastic neoplasms (MDS) have a risk of secondary acute myeloid leukemia (sAML) transformation, but previous studies on the paired samples at both MDS and sAML were very rare. This study aimed to investigate the genetic changes during the progression from MDS to sAML by comparing both phases of MDS at diagnosis and sAML in the same individuals. Seventy-nine paired matched samples of MDS at diagnosis and sAML phase were examined for 32 gene mutations commonly occurring in myeloid neoplasms, including epigenetic regulators, cohesin complex, spliceosome complex, signaling pathway, tumor suppressors, and transcription factors by next-generation sequencing. The acquisition of gene mutations involving signaling pathway and transcription factors was significantly more frequent during the progression to sAML compared to other groups of genes. Mutations involving epigenetic regulators, cohesin complex, and spliceosome complex were generally stable or expanded when disease progressed. Loss of gene mutations was rare, and all mutations showed no apparent decline in their variant allele frequencies except STAG2 mutation. RUNX1 mutations were characterized by acquisition or clonal expansion with no loss or decline during disease progression. TP53 mutations exhibit unique mutational complexity and evolutionary patterns. The dynamic distribution pattern of various gene mutations remained similar regardless of BM blast counts at MDS or the rate of disease progression. Our results demonstrated a distinct pattern of clonal changes in different groups of gene mutations during the progression from MDS to sAML.
Ou et al. (Sun,) studied this question.