The retrospective analysis of paired DNA samples from MDS and leukemic phases, obtained four months apart, using both targeted next-generation sequencing and single nucleotide polymorphism array, indicated swift alterations in the genomic profile, being suggested that the leukemic clone emerged from the clone harboring homozygous <i>TET2</i> and heterozygous <i>SRSF2</i> variants that acquired <i>RUNX1</i>, <i>BCOR</i>, <i>BCORL1</i> likely pathogenic mutations and trisomy 13. This evidence concerns the gene RUNX1 and myelodysplastic syndrome.