Skip to main content
PMC home page
Journal of the National Medical Association logoLink to Journal of the National Medical Association
. 1994 Feb;86(2):129–135.

Erythropoietin: a review.

D M Ridley 1, F Dawkins 1, E Perlin 1
PMCID: PMC2568173  PMID: 8169988

Abstract

The fact that a plasma factor was responsible for the stimulation of red cell production has been known for more than 35 years. However, it is only recently that the gene responsible for its production and its molecular structure has been identified. Furthermore, recombinant human erythropoietin is now available for clinical use. This article details the molecular biology and clinical pharmacology of this remarkable growth factor.

Full text

PDF
129

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beguin Y., Lipscei G., Thoumsin H., Fillet G. Blunted erythropoietin production and decreased erythropoiesis in early pregnancy. Blood. 1991 Jul 1;78(1):89–93. [PubMed] [Google Scholar]
  2. Bowen D. T., Jacobs A., Cotes P. M., Lewis T. C. Serum erythropoietin and erythropoiesis in patients with myelodysplastic syndromes. Eur J Haematol. 1990 Jan;44(1):30–32. doi: 10.1111/j.1600-0609.1990.tb00343.x. [DOI] [PubMed] [Google Scholar]
  3. Bowen D., Ehmer B., Neubert P., Lewis T., Jacobs A. The clearance of a single i.v. bolus of recombinant human erythropoietin from the serum of patients with myelodysplastic syndromes and its effects on erythropoiesis. Exp Hematol. 1991 Aug;19(7):613–616. [PubMed] [Google Scholar]
  4. Cazzola M., Ponchio L., Beguin Y., Rosti V., Bergamaschi G., Liberato N. L., Fregoni V., Nalli G., Barosi G., Ascari E. Subcutaneous erythropoietin for treatment of refractory anemia in hematologic disorders. Results of a phase I/II clinical trial. Blood. 1992 Jan 1;79(1):29–37. [PubMed] [Google Scholar]
  5. Cotes P. M., Doré C. J., Yin J. A., Lewis S. M., Messinezy M., Pearson T. C., Reid C. Determination of serum immunoreactive erythropoietin in the investigation of erythrocytosis. N Engl J Med. 1986 Jul 31;315(5):283–287. doi: 10.1056/NEJM198607313150503. [DOI] [PubMed] [Google Scholar]
  6. D'Andrea A. D., Lodish H. F., Wong G. G. Expression cloning of the murine erythropoietin receptor. Cell. 1989 Apr 21;57(2):277–285. doi: 10.1016/0092-8674(89)90965-3. [DOI] [PubMed] [Google Scholar]
  7. D'Andrea A. D., Zon L. I. Erythropoietin receptor. Subunit structure and activation. J Clin Invest. 1990 Sep;86(3):681–687. doi: 10.1172/JCI114763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dessypris E. N., Gleaton J. H., Armstrong O. L. Effect of human recombinant erythropoietin on human marrow megakaryocyte colony formation in vitro. Br J Haematol. 1987 Mar;65(3):265–269. doi: 10.1111/j.1365-2141.1987.tb06852.x. [DOI] [PubMed] [Google Scholar]
  9. Erslev A. J. Erythropoietin titers in health and disease. Semin Hematol. 1991 Jul;28(3 Suppl 3):2–8. [PubMed] [Google Scholar]
  10. Erslev A. J. Erythropoietin. N Engl J Med. 1991 May 9;324(19):1339–1344. doi: 10.1056/NEJM199105093241907. [DOI] [PubMed] [Google Scholar]
  11. Eschbach J. W., Egrie J. C., Downing M. R., Browne J. K., Adamson J. W. The safety of epoetin-alpha: results of clinical trials in the United States. Contrib Nephrol. 1991;88:72–80. doi: 10.1159/000419517. [DOI] [PubMed] [Google Scholar]
  12. Eschbach J. W., Kelly M. R., Haley N. R., Abels R. I., Adamson J. W. Treatment of the anemia of progressive renal failure with recombinant human erythropoietin. N Engl J Med. 1989 Jul 20;321(3):158–163. doi: 10.1056/NEJM198907203210305. [DOI] [PubMed] [Google Scholar]
  13. Evans R. W., Rader B., Manninen D. L. The quality of life of hemodialysis recipients treated with recombinant human erythropoietin. Cooperative Multicenter EPO Clinical Trial Group. JAMA. 1990 Feb 9;263(6):825–830. [PubMed] [Google Scholar]
  14. Fagg B. Is erythropoietin the only factor which regulates late erythroid differentiation? Nature. 1981 Jan 15;289(5794):184–186. doi: 10.1038/289184a0. [DOI] [PubMed] [Google Scholar]
  15. Flaharty K. K., Caro J., Erslev A., Whalen J. J., Morris E. M., Bjornsson T. D., Vlasses P. H. Pharmacokinetics and erythropoietic response to human recombinant erythropoietin in healthy men. Clin Pharmacol Ther. 1990 May;47(5):557–564. doi: 10.1038/clpt.1990.76. [DOI] [PubMed] [Google Scholar]
  16. Goldberg M. A., Dunning S. P., Bunn H. F. Regulation of the erythropoietin gene: evidence that the oxygen sensor is a heme protein. Science. 1988 Dec 9;242(4884):1412–1415. doi: 10.1126/science.2849206. [DOI] [PubMed] [Google Scholar]
  17. Goldberg M. A., Gaut C. C., Schapira L., Antin J. H., Ransil B. J., Antman K. H., Eder J. P., McGarigle C. J., Bunn H. F. Erythropoietin gene regulation: from the laboratory to the bedside. Contrib Nephrol. 1991;88:35–47. doi: 10.1159/000419514. [DOI] [PubMed] [Google Scholar]
  18. Goldwasser E., Beru N. The regulation of erythropoietin gene expression. Contrib Nephrol. 1991;88:2–9. [PubMed] [Google Scholar]
  19. Gregory C. J. Erythropoietin sensitivity as a differentiation marker in the hemopoietic system: studies of three erythropoietic colony responses in culture. J Cell Physiol. 1976 Oct;89(2):289–301. doi: 10.1002/jcp.1040890212. [DOI] [PubMed] [Google Scholar]
  20. Gregory C. J., McCulloch E. A., Till J. E. Erythropoietic progenitors capable of colony formation in culture: state of differentiation. J Cell Physiol. 1973 Jun;81(3):411–420. doi: 10.1002/jcp.1040810313. [DOI] [PubMed] [Google Scholar]
  21. Jackson C. W., Simone J. V., Edwards C. C. The relationship of anemia and thrombocytosis. J Lab Clin Med. 1974 Sep;84(3):357–368. [PubMed] [Google Scholar]
  22. Jacobs A., Culligan D., Bowen D. Erythropoietin and the myelodysplastic syndrome. Contrib Nephrol. 1991;88:266–270. doi: 10.1159/000419535. [DOI] [PubMed] [Google Scholar]
  23. Jacobs A., Janowska-Wieczorek A., Caro J., Bowen D. T., Lewis T. Circulating erythropoietin in patients with myelodysplastic syndromes. Br J Haematol. 1989 Sep;73(1):36–39. doi: 10.1111/j.1365-2141.1989.tb00215.x. [DOI] [PubMed] [Google Scholar]
  24. Kennedy W. L., Alpen E. L., Garcia J. F. Erythroid colony production in vitro as a function of exposure time to erythropoietin. Blood Cells. 1978;4(1-2):143–154. [PubMed] [Google Scholar]
  25. Krantz S. B., Goldwasser E. Specific binding of erythropoietin to spleen cells infected with the anemia strain of Friend virus. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7574–7578. doi: 10.1073/pnas.81.23.7574. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Macdougall I. C., Hutton R. D., Coles G. A., Williams J. D. The use of erythropoietin in renal failure. Postgrad Med J. 1991 Jan;67(783):9–15. doi: 10.1136/pgmj.67.783.9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Macdougall I. C., Roberts D. E., Neubert P., Dharmasena A. D., Coles G. A., Williams J. D. Pharmacokinetics of recombinant human erythropoietin in patients on continuous ambulatory peritoneal dialysis. Lancet. 1989 Feb 25;1(8635):425–427. doi: 10.1016/s0140-6736(89)90014-7. [DOI] [PubMed] [Google Scholar]
  28. Magli M. C., Iscove N. N., Odartchenko N. Transient nature of early haematopoietic spleen colonies. Nature. 1982 Feb 11;295(5849):527–529. doi: 10.1038/295527a0. [DOI] [PubMed] [Google Scholar]
  29. Maxwell A. P., Lappin T. R., Johnston C. F., Bridges J. M., McGeown M. G. Erythropoietin production in kidney tubular cells. Br J Haematol. 1990 Apr;74(4):535–539. doi: 10.1111/j.1365-2141.1990.tb06347.x. [DOI] [PubMed] [Google Scholar]
  30. McDonald T. P., Cottrell M. B., Clift R. E., Cullen W. C., Lin F. K. High doses of recombinant erythropoietin stimulate platelet production in mice. Exp Hematol. 1987 Jul;15(6):719–721. [PubMed] [Google Scholar]
  31. McGraw J. P. Use of recombinant human erythropoietin in a Jehovah's Witness. J Trauma. 1991 Jul;31(7):1017–1018. [PubMed] [Google Scholar]
  32. Miles S. A. The use of hematopoietic growth factors in HIV infection and AIDS-related malignancies. Cancer Invest. 1991;9(2):229–238. doi: 10.3109/07357909109044233. [DOI] [PubMed] [Google Scholar]
  33. Misiti J., Spivak J. L. Erythropoiesis in vitro. Role of calcium. J Clin Invest. 1979 Dec;64(6):1573–1579. doi: 10.1172/JCI109618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Nielsen O. J. Determination of human erythropoietin by radioimmunoassay. Method and clinical data. Clin Chim Acta. 1988 Sep 15;176(3):303–313. doi: 10.1016/0009-8981(88)90189-1. [DOI] [PubMed] [Google Scholar]
  35. Oster W., Herrmann F., Gamm H., Zeile G., Lindemann A., Müller G., Brune T., Kraemer H. P., Mertelsmann R. Erythropoietin for the treatment of anemia of malignancy associated with neoplastic bone marrow infiltration. J Clin Oncol. 1990 Jun;8(6):956–962. doi: 10.1200/JCO.1990.8.6.956. [DOI] [PubMed] [Google Scholar]
  36. Radtke H. W., Claussner A., Erbes P. M., Scheuermann E. H., Schoeppe W., Koch K. M. Serum erythropoietin concentration in chronic renal failure: relationship to degree of anemia and excretory renal function. Blood. 1979 Oct;54(4):877–884. [PubMed] [Google Scholar]
  37. Reissmann K. R., Udupa K. B. Effect of erythropoietin on proliferation of erythropoietin-responsive cells. Cell Tissue Kinet. 1972 Nov;5(6):481–489. doi: 10.1111/j.1365-2184.1972.tb00386.x. [DOI] [PubMed] [Google Scholar]
  38. SCHOOLEY J. C. RESPONSIVENESS OF HEMATOPOIETIC TISSUE TO ERYTHROPOIETIN IN RELATION TO THE TIME OF ADMINISTRATION AND DURATION OF ACTION OF THE HORMONE. Blood. 1965 May;25:795–808. [PubMed] [Google Scholar]
  39. Samtleben W., Ehmer B., Lutz-Knochenhauer I., Hagmann C., Scigalla P., Gurland H. J. Side effects during recombinant human erythropoietin therapy in 2,000 ESRD patients. Contrib Nephrol. 1991;88:107–117. doi: 10.1159/000419520. [DOI] [PubMed] [Google Scholar]
  40. Sherwood J. B., Goldwasser E., Chilcote R., Carmichael L. D., Nagel R. L. Sickle cell anemia patients have low erythropoietin levels for their degree of anemia. Blood. 1986 Jan;67(1):46–49. [PubMed] [Google Scholar]
  41. Sobota J. T. The role of recombinant human erythropoietin in homologous transfusion avoidance. Contrib Nephrol. 1991;88:334–350. doi: 10.1159/000419543. [DOI] [PubMed] [Google Scholar]
  42. Spivak J. L. The mechanism of action of erythropoietin. Int J Cell Cloning. 1986 May;4(3):139–166. doi: 10.1002/stem.5530040302. [DOI] [PubMed] [Google Scholar]
  43. Steinhauer H. B., Lubrich-Birkner I., Dreyling K. W., Schollmeyer P. Effect of human recombinant erythropoietin on anaemia and dialysis efficiency in patients undergoing continuous ambulatory peritoneal dialysis. Eur J Clin Invest. 1991 Feb;21(1):47–52. doi: 10.1111/j.1365-2362.1991.tb01357.x. [DOI] [PubMed] [Google Scholar]
  44. Stephenson J. R., Axelrad A. A., McLeod D. L., Shreeve M. M. Induction of colonies of hemoglobin-synthesizing cells by erythropoietin in vitro. Proc Natl Acad Sci U S A. 1971 Jul;68(7):1542–1546. doi: 10.1073/pnas.68.7.1542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Udupa K. B., Reissmann K. R. Cell kinetics of erythroid colony-forming cells (CFU-E) studied by hydroxyurea injections and sedimentation velocity profile. Exp Hematol. 1978 Apr;6(4):398–404. [PubMed] [Google Scholar]
  46. Zappacosta A. R., Perras S. T., Bell A. Weekly subcutaneous recombinant human erythropoietin corrects anemia of progressive renal failure. Am J Med. 1991 Sep;91(3):229–232. doi: 10.1016/0002-9343(91)90120-m. [DOI] [PubMed] [Google Scholar]
  47. al-Momen A. K. Recombinant human erythropoietin induced rapid healing of a chronic leg ulcer in a patient with sickle cell disease. Acta Haematol. 1991;86(1):46–48. doi: 10.1159/000204799. [DOI] [PubMed] [Google Scholar]
  48. van Kamp H., Prinsze-Postema T. C., Kluin P. M., den Ottolander G. J., Beverstock G. C., Willemze R., Fibbe W. E. Effect of subcutaneously administered human recombinant erythropoietin on erythropoiesis in patients with myelodysplasia. Br J Haematol. 1991 Aug;78(4):488–493. doi: 10.1111/j.1365-2141.1991.tb04477.x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of the National Medical Association are provided here courtesy of National Medical Association

RESOURCES