Figure 3. The type and the number of mutations determine the phenotype of the disease.

Boundaries between diseases are not easy to determine and could be dependent on the types or the number of mutations. Proliferation is driven mainly by signaling mutations ( JAK2, CALR, and MPL) while most of the mutations in epigenetic regulators and spliceosome components lead to differentiation defects. Thus, it can be considered that primary myelofibrosis (PMF) is not a pure myeloproliferative neoplasm (MPN) but a disorder with both myeloproliferative and myelodysplastic components. The heterogeneity of the disease and its prognosis are dependent on the respective levels of each component, and prognosis is poor if myelodysplastic features are predominant.