EPO receptor gain-of-function causes hereditary polycythemia, alters CD34 cell differentiation and increases circulating endothelial precursors
Authors: Donghoon Yoon
Domenico Roberti
Valeria Cucciolla
Adriana Borriello
Francesco Bertolini
Patrizia Mancuso
Maria Domenica Cappellini
Francesca Rossi
Marcella Ferraro
Annunziata Tramontano
Ines Martin-Padura
Silverio Perrotta
Giovanni Amendola
Anna Rita Migliaccio
Adriana Oliva
Fulvio Della Ragione
Bruno Nobili
Josef T Prchal
Luisa Ronzoni
Anna Chiara Scudieri
Journal: PloS one (2010)
Discipline: Multidisciplinary
Keywords: EPOR mutation; polycythemia; erythropoietin receptor; endothelial precursors; CD34(+) cells
Affiliations: Department of Pediatrics, Second University of Naples, Naples, Italy.

Abstract:  Background: Gain-of-function of erythropoietin receptor (EPOR) mutations represent the major cause of primary hereditary polycythemia. EPOR is also found in non-erythroid tissues, although its physiological role is still undefined. Methodology/principal findings: We describe a family with polycythemia due to a heterozygous mutation of the EPOR gene that causes a G--&gt;T change at nucleotide 1251 of exon 8. The novel EPOR G1251T mutation results in the replacement of a glutamate residue by a stop codon at amino acid 393. Differently from polycythemia vera, EPOR G1251T CD34(+) cells proliferate and differentiate towards the erythroid phenotype in the presence of minimal amounts of EPO. Moreover, the affected individuals show a 20-fold increase of circulating endothelial precursors. The analysis of erythroid precursor membranes demonstrates a heretofore undescribed accumulation of the truncated EPOR, probably due to the absence of residues involved in the EPO-dependent receptor internalization and degradation. Mutated receptor expression in EPOR-negative cells results in EPOR and Stat5 phosphorylation. Moreover, patient erythroid precursors present an increased activation of EPOR and its effectors, including Stat5 and Erk1/2 pathway. Conclusions/significance: Our data provide an unanticipated mechanism for autosomal dominant inherited polycythemia due to a heterozygous EPOR mutation and suggest a regulatory role of EPO/EPOR pathway in human circulating endothelial precursors homeostasis. 

Retracted: Yes

PubPeer comments:
 It comes to our notice that the images in Figure 5a for DOX MSLP, as highlighted in the red frame, ![file] are extremely the same images in one article by the same authors (same co-first author and same corresponding author)in Nanoscale, 2020, 12, 5380,DOI: 10.1039 c9nr10574c, Figure 6b DiD, as hightlighted in the red frame. ![file] , 
 Thank you for your careful point out, and we are also very sorry for the occurrence of such low-level errors. We discovered this error when the article was first printed on May 2. Due to the reasons of concurrent experiments and data preservation, the experimental results (Fig. 5a) used in the tumor spheroids permeability experiment were confused with other subjects we conducted in the same period. This accident was causes by saving wrong similar file names during processing the image data. We immediately emailed the Journal editor to request a corrigendum on May 2. We received a reply from the editor on May 7, asking us to fill out a corrigendum and send it to the publisher. We contacted the publisher and filled out a corrigendum. We are now waiting for corrigendum online. We attach the emails with the editor and publisher of the Journal. ![file] ![file] , 
 #1 Thank you for pointing out, we explained the reasons below. , 
 A corrigendum about the wrong pictures in the article has been made in the same Journal. https: doi.org 10.1016 j.colsurfb.2021.111733 , 
 https: www.sciencedirect.com science article pii S0927776521003684?via%3Dihub ,