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

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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.

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Acknowledgments

This study was supported by a grant from the Natural Science Key Program of Science and Technology Commission Foundation of Tianjin of China (nos. 08JCZDJC19100 and 09JCZDJC17300), and the Ph.D. Programs Foundation of Ministry of Education of China (no. 20091106110038).

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Authors and Affiliations

  1. State Key Laboratory of Experimental Hematology, Institute of Hematology and Hospital of Blood Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing Road 288, Tianjin, 300020, China

    Ronghua Hu, Yan Yan, Qinghua Li, Yani Lin, Weina Jin, Huawen Li, Ying Lu & Tianxiang Pang

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  1. Ronghua Hu
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  2. Yan Yan
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  3. Qinghua Li
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  4. Yani Lin
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  5. Weina Jin
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  6. Huawen Li
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  7. Ying Lu
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  8. Tianxiang Pang
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Correspondence to Tianxiang Pang.

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R. Hu and Y. Yan contributed equally to this work.

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Hu, R., Yan, Y., Li, Q. et al. Increased drug efflux along with midkine gene high expression in childhood B-lineage acute lymphoblastic leukemia cells. Int J Hematol 92, 105–110 (2010). https://doi.org/10.1007/s12185-010-0613-x

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  • DOI: https://doi.org/10.1007/s12185-010-0613-x

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