Fortunately, MPNs are slowly growing neoplasms which have several transitional stages in the biological continuum from the earliest cancer stages (eg JAK2V617F and CALR mutations in the background population as clonal hematopoiesis of indeterminate potential (CHIP)) to ET, PV, and the advanced cancer stage with myelofibrosis, bone marrow failure, and huge splenomegaly before terminal leukemic transformation. The gene discussed is CALR; the disease is cancer.