Selective Expression of mRNA Coding for the Truncated Form of Erythropoietin Receptor in Hematopoietic Cells and Its Decrease in Patients With Polycythemia Vera
Shigeru Chiba,
Tokiharu Takahashi,
Kenichi Takeshita,
Jun Minowada,
Yoshio Yazaki,
Frank H. Ruddle, and
Hisamaru Hirai
From the Third Department of Internal Medicine and Department of Cell Therapy and Transplantation Medicine, Faculty of Medicine, University of Tokyo, Tokyo Japan; Departments of Biology, Human Genetics, and Medicine, Yale University, New Haven, CT; Division of Hematology, Department of Internal Medicine, New York University Medical Center, New York, NY; and Fujisaki Cell Center, Hayashibara Biochemical Research Laboratories, Okayama, Japan.
The mRNA encoding full-length erythropoietin (EPO) receptor (EPOR-F ) comprises exons I through VIII. Another membrane-bound EPOR (EPOR-T) isoform has a truncated cytoplasmic region and is encoded by the mRNA containing unspliced intron VII (EPOR-T mRNA). EPOR-T is believed to have a dominantly negative function against EPOR-F. We show that EPOR-T mRNA is markedly decreased in the blood cells of patients with polycythemia vera (PV). We also show that EPOR-T mRNA is not detected in erythroid/megakaryocytic leukemia cell lines, but is expressed in nonerythroid/nonmegakaryocytic lines, suggesting the presence of a cell type-specific system by which intron VII of the EPOR transcript is spliced. Deregulation of this splicing system in early hematopoietic progenitors possibly explains the profound decrease in EPOR-T mRNA and consequent pathophysiology of PV.
Blood, Vol. 90 No. 1 (July 1), 1997:
pp. 97-104
© 1997 by The American Society of Hematology.
