The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

On the role of the retinoblastoma tumor suppressor gene in hematopoietic differentiation

På svenska

Author

Summary, in English

The aim of this study was to investigate the role of some tumor suppressor gene products (with emphasis on the retinoblastoma suppressor gene product) in the regulation of differentiation and proliferation in leukemic and normal hematopoietic cells. For this purpose, the expression of the tumor suppressor genes RB, p53 and p16 were artificially altered. Cells used were human leukemic cell lines and isolated human bone marrow progenitors. The results show that the retinoblastoma protein, pRb, is involved in the differentiation of human leukemic cell lines, probably through mechanisms that are separate from pRb’s well established ability to regulate cell cycle progression. Suppression of pRb by antisense RB oligonucleotides in isolated bone marrow cells inhibited the monocytic maturation but simultaneously promoted the alternative neutrophilic pathway, indicating an important role for pRb in human myeloid lineage commitment. Again, this effect of pRb seemed mediated through mechanisms distinct from pRb’s cell cycle regulatory potential. Artificial over expression of p53 in leukemic cells lacking p53 made them more responsive to differentiation signals. Arrest of cell proliferation did not enhance the capacity for differentiation, suggesting that cell differentiation and cell cycle regulation are separately regulated processes.

Publishing year

1999

Language

English

Document type

Dissertation

Publisher

Gösta Bergh, Kävlingev 1, S-222 40 Lund, Sweden

Topic

  • Hematology

Keywords

  • antisense
  • leukemia
  • cell cycle
  • differentiation
  • hematopoiesis
  • p16
  • p53
  • tumor suppressor genes
  • RB
  • oligonucleotides
  • Haematology
  • extracellular fluids
  • Hematologi
  • extracellulära vätskor

Status

Published

Supervisor

  • [unknown] [unknown]

ISBN/ISSN/Other

  • ISBN: 91-628-3804-0
  • ISRN: LUMEDW/MEMA--99(1058)--SE

Defence date

23 October 1999

Defence time

10:00

Defence place

Segerfalksalen, Wallenberg Neurocentrum, Lund

Opponent

  • Dan Grandér (MD PhD)