Thermodynamic transitions on metabolism and proliferation of glucocorticoid-treated acute leukemia cells

<p>Glucocorticoids play an essential part in anti-leukemic therapies. Resistance is considered crucial for disease prognosis. Glucocorticoids influence the metabolic properties of the cell and consequently the leukemic cells. We have previously outlined the differences that emerge from glucocorticoid treatment used in various concentrations, and lower concentrations manifested a mitogenic effect. A critical established glucocorticoid action is the apoptotic effect they exert on leukemic cells. However, little is known about the molecular response of malignant cells following glucocorticoid exposure. Even less is known about the cell proliferation dynamics governing leukemic cells under glucocorticoid influence. Growth and metabolic features are assumed to be of nonlinear nature. A model based prediction of glucocorticoid effects is derived by applying a non-linear fitting approximation to the measured parameters. Additionally, borrowing principles from the metabolic engineering and thermodynamics disciplines, we calculated the required energetics for cell proliferation under prednisolone treatment. Finally, we utilized a previously reported microarray dataset, to examine whether the predicted and measured parameters of the metabolism and proliferation under glucocorticoids are reflected in gene expression. Hence, making such an approach more pragmatic since those genes could shed light into the mechanisms of glucocorticoid-induced apoptotic resistance action, and subsequently identify novel targets for more efficient glucocorticoid treatments. We have eventually attempted to answer the basic question of what the thermodynamic mechanisms in the transition of the cell population from one state to the next are.</p