Increased drug efflux along with midkine gene high expression in childhood B-lineage acute lymphoblastic leukemia cells

Abstract

Multidrug resistance (MDR) induced by drug efflux has been identified as the major clinical obstacle in the treatment of childhood acute lymphoblastic leukemia (ALL). To explore the possible effects of midkine (MK) gene on the chemotherapeutic drugs efflux, we examined the MK gene expression in 139 B-lineage ALL patients and 15 children with nonmalignant hematological diseases. Meanwhile, we detected the degree of drug accumulation in 30 progressing B-lineage ALL patients and the 15 control individuals (as control). The results showed that the significant statistic difference in MK gene expression was found among the normal group, the complete remission (CR), and progressing B-lineage ALL patients (p < 0.01). In the Rhodamine 123 (Rh123) efflux test, mean fluorescence intensity (MFI) in the leukemia cells was obviously lower than that in normal pre-B cells (p < 0.01). Furthermore, there was an evident negative correlation between the MFI and MK mRNA expression (r = -0.869, p < 0.001) but no correlation with the MDR1 mRNA expression (p > 0.05). We concluded that there was powerful drug efflux ability in lymphoblastic leukemia cells with high MK gene expression. MK gene may take part in multidrug resistance.