In contrast to physiological transient signaling, persistent STAT5 activation is a hallmark of many hematological malignancies including myeloproliferative neoplasms (MPNs) such as polycythemia vera (PV, JAK2V617F), essential thrombocythemia (ET, JAK2V617F), systemic mastocytosis (SM, cKITD816V), acute myeloid leukemia (AML, FLT3-ITD) and chronic myeloid leukemia (CML, BCR-ABL) [3]. The gene discussed is STAT5B; the disease is systemic mastocytosis.