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: Katarina Kapralova, Lucie Lanikova, Felipe Lorenzo, Jihyun Song, Monika Horvathova, Vladimir Divoky, Josef T Prchal
• Journal: Blood (Blood) Vol. 123 Issue 3 Pg. 391-4 (Jan 16 2014) ISSN: 1528-0020 [Electronic] United States
• PMID: 24297870 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Core Binding Factor Alpha 2 Subunit
• HIF1A protein, human
• Hif1a protein, mouse
• Hypoxia-Inducible Factor 1, alpha Subunit
• NF-E2 Transcription Factor, p45 Subunit
• NFE2 protein, human
• Nfe2 protein, mouse
• RUNX1 protein, human
• Runx1 protein, mouse
• Erythropoietin

Topics

• Animals
• Cell Hypoxia
• Core Binding Factor Alpha 2 Subunit (genetics, metabolism)
• Erythropoietin (metabolism)
• Gene Expression Regulation
• Granulocytes (cytology)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (metabolism)
• Leukocytes, Mononuclear (cytology)
• Mice
• Mice, Transgenic
• Mutation
• Myeloproliferative Disorders (genetics, metabolism)
• NF-E2 Transcription Factor, p45 Subunit (genetics, metabolism)
• Polycythemia (genetics, metabolism)
• Signal Transduction