Effects of bryostatin-1 on chronic myeloid leukaemia-derived haematopoietic progenitors
| Autor: | J.W. van Oostveen, S.F.T. Thijsen, A.P. Theijsmeijer, K G van der Hem, Gert J. Ossenkoppele, Joan H. Odding, Gerrit-Jan Schuurhuis, Angelika M. Dräger |
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| Přispěvatelé: | VU University medical center |
| Rok vydání: | 1999 |
| Předmět: |
Cancer Research
Bryostatin 1 Fusion Proteins bcr-abl bryostatin Biology chemistry.chemical_compound Lactones FISH hemic and lymphatic diseases Leukemia Myelogenous Chronic BCR-ABL Positive purging medicine Humans Progenitor cell Bryostatin CML In Situ Hybridization Fluorescence Tumor Stem Cell Assay Macrophages CFU-GM LTCIC Regular Article Bryostatins Hematopoietic Stem Cells Molecular biology Antineoplastic Agents Phytogenic Enzyme Activation Haematopoiesis Granulocyte macrophage colony-stimulating factor Oncology chemistry Cell culture Immunology Cytokine secretion Macrolides Stem cell medicine.drug Granulocytes |
| Zdroj: | British Journal of Cancer Thijsen, S F T, Schuurhuis, G J, van Oostveen, J W, Theijsmeijer, A P, van der Hem, K G, Odding, J H, Draeger, A M & Ossenkoppele, G J 1999, ' Effects of bryostatin-1 on chronic myeloid leukaemia-derived haematopoietic progenitors ', British Journal of Cancer, vol. 79, pp. 1406-1412 . https://doi.org/10.1038/sj.bjc.6690225 British Journal of Cancer, 79, 1406-1412. Nature Publishing Group |
| ISSN: | 0007-0920 |
| DOI: | 10.1038/sj.bjc.6690225 |
| Popis: | Bryostatin-1 belongs to the family of macrocyclic lactones isolated from the marine bryozoan Bugula neritina and is a potent activator of protein kinase C (PKC). Bryostatin has been demonstrated to possess both in vivo and in vitro anti-leukaemic potential. In samples derived from chronic myeloid leukaemia (CML) patients, it has been demonstrated that bryostatin-1 induces a macrophage differentiation, suppresses colony growth in vitro and promotes cytokine secretion from accessory cells. We investigated the effect of bryostatin-1 treatment on colony-forming unit–granulocyte macrophage (CFU–GM) capacity in the presence of accessory cells, using mononuclear cells, as well as in the absence of accessory cells using purified CD34-positive cells. Cells were obtained from 14 CML patients as well as from nine controls. Moreover, CD34-positive cells derived from CML samples and controls were analysed for stem cell frequency and ability using the long-term culture initiating cell (LTCIC) assay at limiting dilution. Individual colonies derived from both the CFU–GM and LTCIC assays were analysed for the presence of the bcr–abl gene with fluorescence in situ hybridization (FISH) to evaluate inhibition of malignant colony growth. The results show that at the CFU–GM level bryostatin-1 treatment resulted in only a 1.4-fold higher reduction of CML colony growth as compared to the control samples, both in the presence and in the absence of accessory cells. However, at the LTCIC level a sixfold higher reduction of CML growth was observed as compared to the control samples. Analysis of the LTCICs at limiting dilution indicates that this purging effect is caused by a decrease in output per malignant LTCIC combined with an increase in the normal stem cell frequency. It is concluded that bryostatin-1 selectively inhibits CML growth at the LTCIC level and should be explored as a purging modality in CML. © 1999 Cancer Research Campaign |
| Databáze: | OpenAIRE |
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