Fig. 10. During AMkL associated with Down Syndrome (trisomy 21) development some genes located on chromosome 21, such as HLCS, HMGN1, DYRK1a, RUNX1, BRWD1) affect the epigenetic landscape of the cell through two steps: 1) Global hypomethylation of the entire genome and 2) Local hypermethylation of genes involved in cell proliferation, apoptosis, cell cycle progression and general hematologic development. These two events ultimately result in acquisition of malignant phenotype of the AMkL cell.