Schematic representation of a case of malignant myeloid disease evolving in four stages along one pathway. Clones with different gene mutations (color squares in cells) represent various ratios of the oligoclonal leukemia. The order and nature of the mutations (or genome alterations) is given as an example and may differ from one case to another. However, in contrast to JAK2V617F, which has a mild effect on hematopoietic stem cell (HSC) , TET2 mutation has the property to initiate the amplification of HSC and to pave the way to secondary mutations . Mutations in signaling molecules, which have a major impact on the disease phenotype, will vary with the type of chronic stage, for example it could affect JAK2 in case of MPN, RAS in case of MP-CMML and be absent in case of MDS. MF: myelofibrosis, RAEB: refractory anemia with excess of blasts, AML: acute myeloid leukemia.