They typically occur after acquisition of a MPN-driving mutation, but also occur as early events that facilitate clonal emergence, followed by the acquisition of mutation(s) in JAK2, MPL or CALR. Concomitant mutations do not directly influence the MPN phenotype but are associated with clonal expansion and disease progression, notably secondary myelofibrosis and leukemic transformation (52, 65–67). The gene discussed is CALR; the disease is myeloproliferative neoplasm.