By employing a comprehensive integrative approach for RNA-sequencing (RNA-seq), DNAm, and exon usage analyses, we found that BOS and AML-ASXL1 patient-derived samples shared an upregulation of Wnt-signaling and DNAm mediated de-repression of specific HOX genes - HOXB4 and HOXA11. However, there remain differences in isoform expression analysis, with distinct RUNX3 isoforms expressed in blood from BOS compared to AML-ASXL1 patient samples. Here, RUNX3 is linked to acute myeloid leukemia.