title: Elevated nuclear factor erythroid-2 levels promote epo-independent erythroid maturation and recapitulate the hematopoietic stem cell and common myeloid progenitor expansion observed in polycythemia vera patients.
abstract: The molecular etiology of polycythemia vera (PV) remains incompletely understood. Patients harbor increased numbers of hematopoietic stem cells and display Epo-independent erythroid maturation. However, the molecular mechanism underlying Epo hypersensitivity and stem cell expansion is unclear. We have previously shown that the transcription factor nuclear factor erythroid-2 (NF-E2) is overexpressed in the majority of PV patients. Here we demonstrated that elevation of NF-E2 expression in healthy CD34(+) cells to levels observed in PV caused Epo-independent erythroid maturation and expansion of hematopoietic stem cell (HSC) and common myeloid progenitor (CMP) cell numbers. Silencing NF-E2 in PV patients reverted both aberrancies, demonstrating for the first time that NF-E2 overexpression is both required and sufficient for Epo independence and HSC/CMP expansion in PV.
authors: Department of Hematology/Oncology, University Hospital Freiburg, Center for Clinical Research, Freiburg, Germany.
authors: Ruzhica
authors: R
authors: Bogeska
authors: Heike L
authors: HL
authors: Pahl
mesh_terms: D018952:Antigens, CD34 / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D004920:Erythropoiesis / Q000502:physiology*; D004921:Erythropoietin / Q000378:metabolism; D005434:Flow Cytometry; D015870:Gene Expression / Q000502:physiology; D020868:Gene Silencing; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D023461:Myeloid Progenitor Cells / Q000473:pathology*; D050984:NF-E2 Transcription Factor, p45 Subunit / Q000235:genetics* / Q000378:metabolism; D011087:Polycythemia Vera / Q000209:etiology* / Q000235:genetics / Q000473:pathology
chemical_list: D018952:Antigens, CD34; D050984:NF-E2 Transcription Factor, p45 Subunit; C494692:NFE2 protein, human; D004921:Erythropoietin