Expression of multidrug resistance-associated ABC transporters in B-CLL is independent of ZAP70 status

Alexander Hoellein; Thomas Decker; Christian Bogner; Madlen Oelsner; Stefanie Hauswald; Christian Peschel; Ulrich Keller; Thomas Licht

doi:10.1007/s00432-009-0670-9

Expression of multidrug resistance-associated ABC transporters in B-CLL is independent of ZAP70 status

Alexander Hoellein, Thomas Decker, Christian Bogner, Madlen Oelsner, Stefanie Hauswald, Christian Peschel, Ulrich Keller, Thomas Licht

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Technical University of Munich

Research output: Contribution to journal › Article › peer-review

12 Scopus citations

Abstract

Purpose: 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. Results: 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. Conclusion: The ZAP70 status is independent of the multidrug resistance phenotype in CLL.

Original language	English
Pages (from-to)	403-410
Number of pages	8
Journal	Journal of Cancer Research and Clinical Oncology
Volume	136
Issue number	3
DOIs	https://doi.org/10.1007/s00432-009-0670-9
State	Published - Mar 2010

Keywords

ABC transporter
CLL
Multidrug resistance
ZAP70

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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title = "Expression of multidrug resistance-associated ABC transporters in B-CLL is independent of ZAP70 status",

abstract = "Purpose: 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. Results: 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. Conclusion: The ZAP70 status is independent of the multidrug resistance phenotype in CLL.",

keywords = "ABC transporter, CLL, Multidrug resistance, ZAP70",

author = "Alexander Hoellein and Thomas Decker and Christian Bogner and Madlen Oelsner and Stefanie Hauswald and Christian Peschel and Ulrich Keller and Thomas Licht",

note = "Funding Information: Acknowledgments This work was supported by the German Jos{\'e} 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 Universit{\"a}t M{\"u}nchen, Munich, Germany, for help with statistical analysis.",

year = "2010",

month = mar,

doi = "10.1007/s00432-009-0670-9",

language = "English",

volume = "136",

pages = "403--410",

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TY - JOUR

T1 - Expression of multidrug resistance-associated ABC transporters in B-CLL is independent of ZAP70 status

AU - Hoellein, Alexander

AU - Decker, Thomas

AU - Bogner, Christian

AU - Oelsner, Madlen

AU - Hauswald, Stefanie

AU - Peschel, Christian

AU - Keller, Ulrich

AU - Licht, Thomas

N1 - Funding Information: Acknowledgments 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.

PY - 2010/3

Y1 - 2010/3

N2 - Purpose: 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. Results: 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. Conclusion: The ZAP70 status is independent of the multidrug resistance phenotype in CLL.

AB - Purpose: 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. Results: 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. Conclusion: The ZAP70 status is independent of the multidrug resistance phenotype in CLL.

KW - ABC transporter

KW - CLL

KW - Multidrug resistance

KW - ZAP70

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IS - 3

ER -

Expression of multidrug resistance-associated ABC transporters in B-CLL is independent of ZAP70 status

Abstract

Keywords

UN SDGs

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