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Myeloproliferative neoplasms (MPNs) constitute a group of clonal, malignant hematopoietic dis-orders, which includes polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). Patients present clinically with erythrocytosis and/or thrombocytosis (PV and ET, respectively) or with pan-cytopenia (PMF) and display a propensity to transform to acute leukemia. Despite the discovery of a variety of mutations in MPN patients (Vainchenker et al., 2011), most notably an activating point mutation in the JAK2 kinase (JAK2V617F; Baxter et al., 2005; James et al., 2005; Kralovics et al., 2005), the pathophysiology of these disorders remains in-completely understood. Consequently, at present, no curative treatment exists besides bone mar-row transplantation, which in this patient popu-lation is associated with considerable morbidity and mortality. We have shown that expression of the he-matopoietic transcription factor nuclear factor erythroid-2 (NF-E2) is elevated in MPN patients irrespective of the presence or absence of the JAK2V617F mutation (Goerttler et al., 2005; Wang et al., 2010). Based on this observation, we have generated a novel murine model for MPN by overexpressing NF-E2 in transgenic mice (Kaufmann et al., 2012). NF-E2–overexpressing mice display many MPN features including thrombocytosis, leukocytosis, Epo-independent colony formation, characteristic bone marrow histology, expansion of stem and progenitor compartments, and spontaneous transformation to acute myeloid leukemia (AML; Kaufmann et al., 2012). During AML transformation, NF-E2 transgenic mice acquire recurrent ge-netic alterations, particularly a gain of genetic material corresponding to human chromo-some 8, which is also frequently observed in MPN patients and is associated with a higher rate of transformation to acute leukemia (Hussein et al., 2009). These data have estab-lished a role for aberrant NF-E2 expressio