The Family Members of Mrps Expression and significance in Childhood Acute Lymphoblastic Leukemia

Objective Multidrug resistance-associated proteins 1 to 6 have been reported involved in a large number of tumors and have a close correlation with tumor multi-drug resistance. In this work, we detect the MRP2-6 genes expression in childhood acute lymphoblastic leukemia (ALL) by Q-RT-PCR and explore their clinical significance.

Methods 156 patients at different stages of ALL were enrolled in this study and treated by the protocol (CCLG-2008) during 2012 to 2013, including 67 cases at initial stage, 70 cases at complete remission, and 9 cases at relapse, 10 patients diagnosed as idiopathic thrombocytopenic purpura (ITP) as control. MRP1-6 genes’ expressions were detected using real-time quantitative PCR (QRT-PCR)and their clinical significance was analyzed by the SPSS software 16.0. P value below 0.05 was regarded as statistic significance.

Results The median expression of MRP1 was 5.82 and 8.49 for initial and relapse group,respectively, which was statistic higher than that at complete remission, the latter was 1.99. MRP1 expression level had close correlation with ALL risk, the median of MRP1 expression was 4.28, 5.62 and 7.56 for standard-risk group (SR), intermediate-risk group (IR) and high-risk group (HR), respectively. Initial ALL children were divided into two groups including high expression group and low expression group by the median expression, the rate of sensitivity of blast cells to prednisone on 7th day was 70.6% in high expression group (n=34), which was statistic lower than that in low expression group which was 90.9% (n=33, P=0.035). The rate of complete remission on 33th day in high expression group was 64.7%, while 87.9% in low expression group, which showed a significant difference between them (P=0.026). The rate of complete remission on 15th day in high expression group was 68.8%, and 69.7% in low expression group, which showed no significance between them (P=0.664). The transcription level of MRP1 in initial group of T-ALL (median=7.71) was statistic higher than that in B-ALL (median=5.18) (P=0.007). Correlation analysis indicated that mRNA expression level of MRP1 didn’t show any relationship with gender, age, WBC count, hemoglobin, platelet and blast percentage in bone narrow and peripheral blood at diagnosis.

The median expression of MRP2 at initial stage was highest, higher than that at relapse and complete remission, but did not reach statistic significance. However, the median expression of MRP3 at initial stage was highest and statistic higher than complete remission. MRP4 and MRP5 showed a similar pattern in their expression, namely, high expression for relapse, intermediate expression for initial stage and low expression at complete remission which reached statistic significance. The median expression of MRP6 for relapse was 2.003, which was higher than initial and complete remission group, but the differences among them were not significant. The median of MRP2 and MRP5 expression for intermediate-risk group (IR) (Median MRP2=4.622, Median MRP5=1.712) was higher than standard- risk group (SR) (Median MRP2=3.279, Median MRP5=1.277) and high risk group (HR) (Median MRP2=2.145, Median MRP5=1.673). However, there was no statistical significance among them. The median of MRP4 expression was increase continually with the risk of ALL, but did not reach statistical significance among them; the median of MRP6 expression for high-risk group (HR) was higher than standard-risk group (0.8812 vs 0.6205) and intermediate-risk group (0.8812 vs 0.4053), but the differences among them were not significant either. Initial ALL children were divided into two group including high expression group and low expression group by median expression, and evaluated their prediction on the treatment response on 7th, 15th and 33th day. The results revealed no significant difference between them, neither between B-ALL and T-ALL. Single factor analysis showed that MRP2 has relationship with platelet count at diagnosis and MRP4 has relationship with gender.

Conclusions In children ALL, the expression of MRP1 is closely related with immunophenotyping, treatment response, hazard level and disease relapse which was a poor biomarker for ALL prognosis. MRP2-6 has a different expression pattern. MRP4 and MRP6 mRNA expression showed a close relation with relapse.