Mathematical model of granulocytopoiesis and chronic myelogenous leukemia

We present a mathematical model of granulocytopoiesis that depends on certain physiologically meaningful parameters. By choosing different values of these parameters, the model describes both the normal process and that in chronic myelogenous leukemia (CML). The model fits all the available experimental data tested. Furthermore, it shows how the CML cells can ultimately outnumber the normal cells and how this process can be very slow. The model provides a quantitative approach to the relationship between proliferation and maturation and resolves the apparent contradiction between decreased proliferation and increased production, by assuming that a greater fraction of CML cells is produced by division rather than by maturation. The model should be helpful in designing experiments to better define the abnormalities of proliferation and maturation in CML and in seeking to define the specific alterations in the cell regulatory networks resulting from the production of the chimeric p210bcr-abl protein characteristic of CML.