Mdr1 gene expression and mutations in Ras proto-oncogenes in acute myeloid leukemia

Abstract

Resistance to cytotoxic therapy and development of refractory disease in acute myeloid leukemia (AML) is frequently associated with the expression of mdr1/P-gp. In the last years many potential signaling pathways leading to modulation of mdr1 expression have been described. Thus, it has been assumed that activated Ras may influence mdr1 expression. This activation can be realized by mutations in the Ras oncogene leading to constitutive signaling. Ras mutations are observed in many human cancers, including AML. Recently, we could show a negative correlation between Ras mutations and mdr1 expression in blast samples of AML patients. Taking this up the potential possibilities of Ras influence on mdr1 activity and their implications on treatment outcome in AML are discussed.