Putative oncogenic role of the erythropoietin receptor in murine and human
erythroleukemia cells
S Chretien, F Moreau-Gachelin, F Apiou, G Courtois, P Mayeux, B Dutrillaux, JP Cartron, S Gisselbrecht and C Lacombe
Institut National de Transfusion Sanguine et Unite INSERM U76, Paris,
France.
To determine whether the erythropoietin receptor (Epo-R) plays a role in
the course of malignant erythropoietic disorders, this gene was studied in
murine and human erythroleukemia cells. An altered Epo-R gene was found in
a murine Friend erythroleukemia cell line, FCL1, due to a spleen
focus-forming virus (SFFV) long terminal repeat insertion within the
noncoding region of the first exon, leading to Epo-R mRNA overexpression. A
similar mechanism of Epo-R activation has previously been described in the
T3CL-2 Friend erythroleukemia cell line. An elevated number of Epo-binding
sites has been observed in two human erythroleukemia cell lines, TF-1 and
UT7. In UT7 cells, homogeneously staining region of the short arm of
chromosome 19 [hsr (19)] was evidenced, which contained an amplification of
the Epo-R gene. This Epo- R gene amplification was confirmed by the
quantification of Southern blots in which the intensity of the Epo-R signal
was compared in UT7 DNA and in DNA from normal cells. The Epo-R gene was
present in UT7 at a mean number of seven to eight copies per cell.
Interestingly, the Epo- R gene was rearranged; the breakpoint region was
located near the 3' end of the gene, 3 kb downstream from the end of the
last exon. Taken together, these results suggest that, in both murine and
human systems, genetic alterations of the Epo-R gene are not rare events
and could be involved in the occurrence of the erythroleukemic process.
Volume 83,
Issue 7,
pp. 1813-1821,
04/01/1994
Copyright © 1994 by The American Society of Hematology
