Enhanced invasiveness in multidrug resistant leukemic cells is associated with overexpression of P-glycoprotein and cellular inhibitor of apoptosis protein

Abstract

Multidrug resistance (MDR) and multi-organ infiltration are the major obstacles to the successful treatment of leukemia. It is known that the drug efflux protein, P-glycoprotein (P-gp), and inhibitors of apoptosis proteins (IAPs) are involved in the MDR of leukemic cells, but their roles in leukemia infiltration have not been clearly elucidated. In this study, leukemic cell lines K562 and HL60 and their MDR variants K562R and HL60R have been used to analyze their infiltrative ability. MDR variants display enhanced invasion compared with parental cells. Results from xenografts in SCID (severe combined immunodeficiancy) mice are consistent with these in vitro observations. Furthermore, P-gp and cIAP are overexpressed and co-localize with protein kinase C-ε (PKC-ε) in MDR variants. Our study shows that overexpression of P-gp and cIAP may enhance the infiltration of leukemic cells.