These pre-LSC contain a limited number of mutations in AML or MDS related genes, such as TET2, DNMT3A, or ASXL1, and have qualitative changes that make them leukemogenic, this is in stark contrast to non-pre-LSC clones in patients with clonal hematopoiesis of indeterminate potential (CHIP; see Discussion and Perspectives below). The gene discussed is DNMT3A; the disease is myelodysplastic syndrome.