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). The gene discussed is JAK2; the disease is leukemia.