In-Vitro Effects of Cytokines on Normal and Myeloid Leukaemic Haemopoiesis

Medicine, Oncology

Mahendra, Premini

University:University of Glasgow

关键词: Medicine, Oncology;   

Others  :  http://theses.gla.ac.uk/75530/1/13832501.pdf

来源: University of Glasgow

【 摘 要 】

The growth of chronic myeloid leukaemic (CML) and acute myeloid leukaemic (AML) cells in vitro and their response to various cytokines were studied and compared to normal peripheral blood and bone marrow cells. In normal mononuclear cells (MNC) the three cytokines [granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony stimulating factor (GM-CSF) and interleukin-3 (IL-3)] had no appreciable difference at stimulating (colony-forming unit granulocyte-macrophage) CFU-GM-formation. By contrast, G-CSF was a more potent stimulator of CFU-CML, than GM-CSF or IL-3. Interleukin-4 (IL-4) augmented G-CSF-induced colony formation of CML chronic phase cells. Transforming growth factor beta1 (TGFbeta1) reduced G-CSF-induced CFU-CML from CML chronic phase (p< 0.005) and blast transformation MNC, but had no effect on normal CFU-GM stimulated by G- CSF. The growth of CML mononuclear cells in vitro could not be correlated to the white cell count or percentage of CD34+ cells present. The mechanisms for the inhibitory effects of TGFbeta1 on CML cells were studied using in-situ hybridisation techniques to demonstrate the expression of the G-CSF and IL-4 receptors. The results suggest that this response is more likely to be due to a difference in signal transduction or protein synthesis rather in transcription.