Key steps during MPN development from normal hematopoiesis following acquisition of an MPN-initiating mutation in a single HSC. The mutant HSC acquires a selective advantage over normal HSC and also promotes myeloid differentiation, eventually leading to a myeloproliferative phenotype. The expanded, abnormal myeloid clone disrupts the bone marrow microenvironment, promoting a self-reinforcing malignant niche that favors MPN stem cells over normal HSC and leads to eventual mobilization of MPN HSC into the peripheral blood (PB).