Relationship between midkine expression and drug efflux in childhood acute lymphoblastic leukemia cells / 中国实验血液学杂志

ABSTRACT

This study was aimed to investigate the expression of midkine gene in childhood acute lymphoblastic leukemia patients (ALL) and to explore the possible effects of midkine gene on the chemotherapeutic drug efflux. Real-time quantitative PCR (RQ-PCR) method was used to determine the expression of midkine at mRNA level in 153 ALL patients and 20 normal children. Meanwhile, laser scanning confocal microscope was used to observe the rhodamine 123 efflux from the mononuclear cells in 30 de novo B-ALL patients and 20 healthy individuals (as control). Flow cytometry was used to detect intracellular mean fluorescence intensity (MFI) which can reflect the degree of drug accumulation. The results showed that the significant statistical difference of midkine gene expression was found among the normal controls, the B-ALL patients in complete remission (CR) and progress with the expression level increasing in turns 0.795 (0.697 - 1.570), 3.012 (0.932 - 5.076) and 12.909 (2.385 - 26.347) respectively (p < 0.01). Expression level of midkine gene in progressing B-ALL group was higher than that in progressing T-ALL (p < 0.01). The rhodamine 123 efflux test revealed that MFI in the leukemia cells was obviously lower than that in normal cells (p < 0.01), furthermore, there was an evident negative correlation between the MFI and MK mRNA expression (r = -0.869, p < 0.001). It is concluded that there is powerful drug efflux ability in lymphoblastic leukemia cells with high midkine gene expression. The midkine may take part in multidrug resistance.