Abstract
The kinetics of proliferation of normal hemopoietic stem cells (HSC) were investigated during the course of leukemia in a rat model for human acute myelocytic leukemia (BNML). The fraction of stem cells in DNA synthesis phase was determined with the hydroxyurea suicide technique followed by modified spleen colony assays on bone marrow, blood and spleen cell suspensions. It was found that, besides a redistribution and an absolute numerical decrease in the total number of HSC (to 45% of the original number), the percentage of cycling HSC decreased significantly as the leukemia progressed. In the bone marrow the S-phase fraction of HSC decreased from 38% to almost zero. Proliferating stem cells are thought to emigrate from the blood and lodge at extramedullary sites. Proliferation of HSC is best preserved in the spleen (in the terminal stage: 32 to 53% in S-phase). However, normal hemopoiesis is still insufficient and the rats die from the consequences of a lack of mature end cells. A possible mechanism underlying the changes and differences in kinetic behaviour of HSC in the various organs studied is discussed.
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