Skip to main content
NCBI home page
Journal of Clinical Pathology logoLink to Journal of Clinical Pathology
. 1986 Aug;39(8):881–890. doi: 10.1136/jcp.39.8.881

Studies of erythroblast function in congenital dyserythropoietic anaemia, type I: evidence of impaired DNA, RNA, and protein synthesis and unbalanced globin chain synthesis in ultrastructurally abnormal cells.

S N Wickramasinghe, M J Pippard
PMCID: PMC500119  PMID: 2427549

Abstract

Two patients with congenital dyserythropoietic anaemia, type I (CDA) were studied. Their blood reticulocytes showed unbalanced globin chain synthesis with increased alpha:beta globin chain synthesis ratios. A high proportion of the erythroblasts displayed the characteristic "Swiss cheese" abnormality of the nuclear chromatin and some also showed cytoplasmic intrusions lined with nuclear membrane within the nucleus. Occasional erythroblast profiles contained intracytoplasmic inclusions that were ultrastructurally indistinguishable from precipitated alpha chains. The technique of combined Feulgen microspectrophotometry and 3H-thymidine autoradiography showed gross abnormalities of proliferation in the early polychromatic erythroblasts. The proliferative abnormalities included an arrest of DNA synthesis after the progress of cells through part of the S phase and the formation of several mononucleate and binucleate cells with hypertetraploid total DNA contents. The bone marrow cells gave a normal deoxyuridine suppressed value, indicating that there was no impairment of the methylation of deoxyuridylate. Electron microscope autoradiographic studies showed that a high proportion of the erythroblasts with the "Swiss cheese" nuclear abnormality suffered from a severe impairment, or arrest of DNA, RNA, and protein synthesis.

Full text

PDF
881

Images in this article

884Image
on p.884
884Image
on p.884
885Image
on p.885
885Image
on p.885
886Image
on p.886
887Image
on p.887
888Image
on p.888

Selected References

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

  1. Alloisio N., Jaccoud P., Dorleac E., Morle L., Philippe N., Margueritte G., Bryon P. A., Delaunay J. Alterations of globin chain synthesis and of red cell membrane proteins in congenital dyserythropoietic anemia I and II. Pediatr Res. 1982 Dec;16(12):1016–1021. doi: 10.1203/00006450-198212000-00010. [DOI] [PubMed] [Google Scholar]
  2. Chanarin I. Management of megaloblastic anaemia in the very young. Br J Haematol. 1983 Jan;53(1):1–3. doi: 10.1111/j.1365-2141.1983.tb01979.x. [DOI] [PubMed] [Google Scholar]
  3. Clegg J. B., Naughton M. A., Weatherball D. J. Abnormal human haemoglobins. Separation and characterization of the alpha and beta chains by chromatography, and the determination of two new variants, hb Chesapeak and hb J (Bangkok). J Mol Biol. 1966 Aug;19(1):91–108. doi: 10.1016/s0022-2836(66)80052-9. [DOI] [PubMed] [Google Scholar]
  4. Heimpel H., Forteza-Vila J., Queisser W., Spiertz E. Electron and light microscopic study of the erythroblasts of patients with congenital dyserythropoietic anemia. Blood. 1971 Mar;37(3):299–310. [PubMed] [Google Scholar]
  5. Hiraoka A., Kanayama Y., Yonezawa T., Kitani T., Tarui S., Hashimoto P. H. Congenital dyserythropoietic anemia type I: a freeze-fracture and thin section electron microscopic study. Blut. 1983 Jun;46(6):329–338. doi: 10.1007/BF00320693. [DOI] [PubMed] [Google Scholar]
  6. Hruby M. A., Mason R. G., Honig G. R. Unbalanced globin chain synthesis in congenital dyserythropoietic anemia. Blood. 1973 Dec;42(6):843–850. [PubMed] [Google Scholar]
  7. Keyserlingk D. G., Boll I., Meuret G. Ultrastruktur der gestörten Erythropoiese bei einer kongenitalen dyserythropoietischen Anëmie. Klin Wochenschr. 1970 Jun 15;48(12):728–736. doi: 10.1007/BF01497130. [DOI] [PubMed] [Google Scholar]
  8. Lewis S. M., Nelson D. A., Pitcher C. S. Clinical and ultrastructural aspects of congenital dyserythropoietic anaemia type I. Br J Haematol. 1972 Jul;23(1):113–119. doi: 10.1111/j.1365-2141.1972.tb03465.x. [DOI] [PubMed] [Google Scholar]
  9. Meuret G., Tschan P., Schlüter G., Keyserlingk D. G., Boll I. DNA , histone-, RNA-, hemoglobin-content and DNA synthesis in erythroblasts in a case of congenital dyserythropoietic anemia type I. Blut. 1972 Jan;24(1):32–41. doi: 10.1007/BF01633140. [DOI] [PubMed] [Google Scholar]
  10. Queisser W., Spiertz E., Jost E., Heimpel H. Proliferation disturbances of erythroblasts in congenital dyserythropoietic anemia type I and II. Acta Haematol. 1971;45(2):65–76. doi: 10.1159/000208608. [DOI] [PubMed] [Google Scholar]
  11. Walford D. M., Deacon R. Alpha-thalassaemia trait in various racial groups in the United Kingdom: characterization of a variant of alpha-thalassaemia in Indians. Br J Haematol. 1976 Oct;34(2):193–206. doi: 10.1111/j.1365-2141.1976.tb00190.x. [DOI] [PubMed] [Google Scholar]
  12. Weatherall D. J., Clegg J. B., Knox-Macaulay H. H., Bunch C., Hopkins C. R., Temperley I. J. A genetically determined disorder with features both of thalassaemia and congenital dyserythropoietic anaemia. Br J Haematol. 1973 Jun;24(6):681–702. doi: 10.1111/j.1365-2141.1973.tb01696.x. [DOI] [PubMed] [Google Scholar]
  13. Weiss D. W. Immunological parameters of host-tumor relationships. V. Introduction: Tumor immunology and immunotherapy in 1977. Isr J Med Sci. 1978 Jan;14(1):1–13. [PubMed] [Google Scholar]
  14. Wickramasinghe S. N., Goudsmit R. Some aspects of the biology of multinucleate and giant mononucleate erythroblasts in a patient with CDA, type III. Br J Haematol. 1979 Apr;41(4):485–495. doi: 10.1111/j.1365-2141.1979.tb05886.x. [DOI] [PubMed] [Google Scholar]
  15. Wickramasinghe S. N., Hughes M. Globin chain precipitation, deranged iron metabolism and dyserythropoiesis in some thalassaemia syndromes. Haematologia (Budap) 1984;17(1):35–55. [PubMed] [Google Scholar]
  16. Wickramasinghe S. N., Hughes M. Ultrastructural studies of erythropoiesis in beta-thalassaemia trait. Br J Haematol. 1980 Nov;46(3):401–407. doi: 10.1111/j.1365-2141.1980.tb05986.x. [DOI] [PubMed] [Google Scholar]
  17. Wickramasinghe S. N., Hughes M., Wasi P., Fucharoen S., Litwinczuk R. A. Ultrastructure and cell cycle distribution of erythropoietic cells in heterozygotes and homozygotes for haemoglobin E. Br J Haematol. 1984 Aug;57(4):685–694. doi: 10.1111/j.1365-2141.1984.tb02946.x. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Publishing Group

RESOURCES