Abstract
Remission induction therapy fails in 20–30% of the patients with acute myeloid leukemia (AML) despite dose intensification and the use of new and more effective drugs. Primary and acquired drug resistance, metabolic or kinetic are a fundamental problem. Expression of the P-glycoprotein in AML is correlated with therapeutic outcome. Randomized clinical studies with Pgp modulators are currently on-going. Ara-C and anthracyclines, are preferentially cytotoxic to proliferating cells. Proliferation induction of leukemia blasts with growth factors in vitro resulted in an increased toxicity of Ara-C and anthracyclines. Normal hematopoietic blast cells with a high Pgp expression are noncycling and less sensitive to anthracyclines, in contrast to the more proliferating cells with a low Pgp expression. Proliferation induction by growth factors results in a down regulation of Pgp expression. Priming of leukemic cells with growth factors in vivo might be promising and randomized clinical studies are warranted.
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Smeets, M., de Witte, T., van der Lely, N., Raymakers, R., Muus, P. (1999). New Developments in the Treatment of Acute Myeloid Leukemia. In: Kaspers, G.J.L., Pieters, R., Veerman, A.J.P. (eds) Drug Resistance in Leukemia and Lymphoma III. Advances in Experimental Medicine and Biology, vol 457. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4811-9_61
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DOI: https://doi.org/10.1007/978-1-4615-4811-9_61
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