Putative oncogenic role of the erythropoietin receptor in murine and human erythroleukemia cells.
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.
Chretien
S
S
Institut National de Transfusion Sanguine et Unité INSERM U76, Paris, France.
Moreau-Gachelin
F
F
Apiou
F
F
Courtois
G
G
Mayeux
P
P
Dutrillaux
B
B
Cartron
J P
JP
Gisselbrecht
S
S
Lacombe
C
C
D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D005784:Gene Amplification; D015321:Gene Rearrangement; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D004915:Leukemia, Erythroblastic, Acute / Q000209:etiology*; D051379:Mice; D008969:Molecular Sequence Data; D017467:Receptors, Erythropoietin / Q000235:genetics* / Q000502:physiology; D012091:Repetitive Sequences, Nucleic Acid; D014407:Tumor Cells, Cultured
D017467:Receptors, Erythropoietin