TET2 mutations are commonly an ancestral mutational event and, as such, constitute a suitable target for intervention in the early stages of hematopoietic stem cell/hematopoietic progenitor cell (HSC/HPC) expansion.Tet2 loss/haploinsufficiency in HSCs/HPCs leads to MDS/MPN development in mice and cooperates with other disease alleles (for example, AML1-ETO orFLT3-ITD) to induce AML15–18. This evidence concerns the gene RUNX1 and myelodysplastic syndrome.