Expression of multidrug resistance-associated ABC transporters in B-CLL is independent of ZAP70 status
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To assess whether the poor prognosis of ZAP70-positive B-cell chronic lymphocytic leukemia (CLL) is associated with the overexpression of ABC transporter genes that are responsible for pleiotropic drug resistance.
Materials and methods
The transcript level of ten drug transporters was analyzed using semiquantitative and quantitative RT-PCR in control hematopoietic cells, in 41 CLL patient samples and in 5 lymphoma cell lines. ZAP70 status was determined by immunoblotting.
Of all analyzed transporters, MDR1, MDR2, MRP1, MRP4, MRP5, and MRP7 were expressed at a significantly higher level in B lymphocytes when compared with other hematopoietic cells in peripheral blood. A subgroup of 41 CLL patient samples showed similar or higher expression of these genes than control B cells, and CLL cells exhibited high expression when compared with multiple lymphoma cell lines. No significant correlation between ZAP70 expression and ABC transporter expression was observed.
The ZAP70 status is independent of the multidrug resistance phenotype in CLL.
KeywordsCLL ABC transporter Multidrug resistance ZAP70
This work was supported by the German José Carreras Leukemia Foundation (Project R04/17 to T. Licht and U. Keller). We are grateful to M. Gottesman, National Cancer Institute, Bethesda, USA, for providing the drug-resistant cell lines KB-3-1 and KB-8-5. We also would like to thank T. Schuster, Institute for Medical Statistics and Epidemiology, Technische Universität München, Munich, Germany, for help with statistical analysis.
Conflict of interest statement
We declare that we have no conflict of interest.
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