title: RUNX1 and NF-E2 upregulation is not specific for MPNs, but is seen in polycythemic disorders with augmented HIF signaling.
abstract: Overexpression of transcription factors runt-related transcription factor 1 (RUNX1) and nuclear factor, erythroid-derived 2 (NF-E2) was reported in granulocytes of patients with polycythemia vera and other myeloproliferative neoplasms (MPNs). Further, a transgenic mouse overexpressing the NF-E2 transgene was reported to be a model of MPN. We hypothesized that increased transcripts of RUNX1 and NF-E2 might characterize other polycythemic states with primary polycythemic features, that is, those with exaggerated erythropoiesis due to augmented erythropoietin (EPO) sensitivity. We tested the expression of RUNX1 and NF-E2 in polycythemic patients of diverse phenotypes and molecular causes. We report that RUNX1 and NF-E2 overexpression is not specific for MPN; these transcripts were also significantly elevated in polycythemias with augmented hypoxia-inducible factor activity whose erythroid progenitors were hypersensitive to EPO. RUNX1 and NF-E2 overexpression was not detected in patients with EPO receptor (EPOR) gain-of-function, suggesting distinct mechanisms by which erythroid progenitors in polycythemias with defects of hypoxia sensing and EPOR mutations exert their EPO hypersensitivity.
authors.affiliation: Division of Hematology, University of Utah, ARUP, and George E. Wahlen Department of Veterans Affairs Medical Center, Salt Lake City, UT; and.
authors.forename: Katarina
authors.initials: K
authors.lastname: Kapralova
authors.forename: Lucie
authors.initials: L
authors.lastname: Lanikova
authors.forename: Felipe
authors.initials: F
authors.lastname: Lorenzo
authors.forename: Jihyun
authors.initials: J
authors.lastname: Song
authors.forename: Monika
authors.initials: M
authors.lastname: Horvathova
authors.forename: Vladimir
authors.initials: V
authors.lastname: Divoky
authors.forename: Josef T
authors.initials: JT
authors.lastname: Prchal
mesh_terms: D000818:Animals; D015687:Cell Hypoxia; D050676:Core Binding Factor Alpha 2 Subunit / Q000235:genetics / Q000378:metabolism*; D004921:Erythropoietin / Q000378:metabolism; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000166:cytology; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D009196:Myeloproliferative Disorders / Q000235:genetics / Q000378:metabolism*; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000235:genetics / Q000378:metabolism*; D011086:Polycythemia / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; C497442:HIF1A protein, human; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D050984:NF-E2 Transcription Factor, p45 Subunit; C494692:NFE2 protein, human; C494693:Nfe2 protein, mouse; C493728:RUNX1 protein, human; C493726:Runx1 protein, mouse; D004921:Erythropoietin