In this study, we performed a thorough, integrative analysis investigating the expression of miRNAs and mRNAs encoded in the DLK1–DIO3 region and compared these data with the methylation status of MEG3-DMR in CD34+ BM cells (i.e., undifferentiated hematopoietic stem/progenitor cells (HSPCs), including blasts) from higher-risk MDS/AML-MRC patients, particularly focusing on the effects of hypomethylating AZA therapy. This evidence concerns the gene MEG3 and acute myeloid leukemia.