JAK2 and essential thrombocythemia: While homozygous loss-of-function mutations in JAK genes can be lethal (JAK1 and JAK2), or highly debilitating (JAK3, severe combined immunodeficiency), heterozygous gain-of-function mutations in JAK genes can give rise to blood disorders known as myeloproliferative neoplasms (MPNs), which include polycythemia vera, primary myelofibrosis, and essential thrombocythemia, and also to leukemias (9).