Expression of MDR1/P-glycoprotein, the multidrug resistance protein MRP, and the lung-resistance protein LRP in multiple myeloma

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Expression of MDR1/P-glycoprotein, the multidrug resistance protein MRP, and the lung-resistance protein LRP in multiple myeloma. / Schwarzenbach, Heidi.

In: MED ONCOL, Vol. 19, No. 2, 01.01.2002, p. 87-104.

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@article{575d570fd646419ea71d78f1c07af9f9,
title = "Expression of MDR1/P-glycoprotein, the multidrug resistance protein MRP, and the lung-resistance protein LRP in multiple myeloma",
abstract = "The purpose of this study was to determine the incidence of three genes associated with multidrug resistance (MDR) in multiple myeloma in relation to treatment status. MDR1/Pgp (P-glycoprotein) expression was detected in 41% of 93 myeloma samples. Generally, the incidence of MDR1/Pgp expression was higher in pretreated samples, and treatments with doxorubicin and/or vincristine were more effective in MDR1/Pgp expression than with alkylating agents. A significant association was observed between MDR1 /Pgp-positiveness and the ability of verapmil to increase doxorubicin sensitivity, suggesting functional relevance of MDR1/Pgp expression. MRP (multidrug resistance protein) expression was detected in 20.5% of 88 myeloma samples, in 26% at the mRNA level analyzed by quantitative reverse transriptase-polymerase chain reaction, and in only 3 of 79 samples by immunohistochemistry. LRP (lung-resistance protein) protein expression was observed in 12.5% of 72 myeloma samples. MRP and LRP expression was similar in samples with and without prior therapy. Approximately 80% of the myeloma samples with detectable mRNA expression of MDRI and MRP exhibited low expression levels corresponding to < 10% of the Pgp- and MRP-overexpressing multidrug-resistant human myeloma cell lines 8226/Dox6 and 8226/DOXint40c, respectively. Some normal bone marrow samples showed higher levels of MRP mRNA as compared to myeloma specimens, whereas MDRI mRNA expression in normal bone marrow was much lower (< or = 5%) than that in 8226/Dox6. These findings indicate a requirement to develop single-cell assays for MRP detection in multiple myeloma that are more sensitive than immunohistochemistry and might be useful to evaluate the incidence of genes associated with MDR.",
keywords = "Antineoplastic Agents, DNA, Complementary, Doxorubicin, Drug Resistance, Multiple, Humans, Multiple Myeloma, Neoplasm Proteins, P-Glycoprotein, Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured, Vault Ribonucleoprotein Particles, Verapamil",
author = "Heidi Schwarzenbach",
year = "2002",
month = jan,
day = "1",
doi = "10.1385/MO:19:2:87",
language = "English",
volume = "19",
pages = "87--104",
journal = "MED ONCOL",
issn = "1357-0560",
publisher = "Humana Press",
number = "2",

}

RIS

TY - JOUR

T1 - Expression of MDR1/P-glycoprotein, the multidrug resistance protein MRP, and the lung-resistance protein LRP in multiple myeloma

AU - Schwarzenbach, Heidi

PY - 2002/1/1

Y1 - 2002/1/1

N2 - The purpose of this study was to determine the incidence of three genes associated with multidrug resistance (MDR) in multiple myeloma in relation to treatment status. MDR1/Pgp (P-glycoprotein) expression was detected in 41% of 93 myeloma samples. Generally, the incidence of MDR1/Pgp expression was higher in pretreated samples, and treatments with doxorubicin and/or vincristine were more effective in MDR1/Pgp expression than with alkylating agents. A significant association was observed between MDR1 /Pgp-positiveness and the ability of verapmil to increase doxorubicin sensitivity, suggesting functional relevance of MDR1/Pgp expression. MRP (multidrug resistance protein) expression was detected in 20.5% of 88 myeloma samples, in 26% at the mRNA level analyzed by quantitative reverse transriptase-polymerase chain reaction, and in only 3 of 79 samples by immunohistochemistry. LRP (lung-resistance protein) protein expression was observed in 12.5% of 72 myeloma samples. MRP and LRP expression was similar in samples with and without prior therapy. Approximately 80% of the myeloma samples with detectable mRNA expression of MDRI and MRP exhibited low expression levels corresponding to < 10% of the Pgp- and MRP-overexpressing multidrug-resistant human myeloma cell lines 8226/Dox6 and 8226/DOXint40c, respectively. Some normal bone marrow samples showed higher levels of MRP mRNA as compared to myeloma specimens, whereas MDRI mRNA expression in normal bone marrow was much lower (< or = 5%) than that in 8226/Dox6. These findings indicate a requirement to develop single-cell assays for MRP detection in multiple myeloma that are more sensitive than immunohistochemistry and might be useful to evaluate the incidence of genes associated with MDR.

AB - The purpose of this study was to determine the incidence of three genes associated with multidrug resistance (MDR) in multiple myeloma in relation to treatment status. MDR1/Pgp (P-glycoprotein) expression was detected in 41% of 93 myeloma samples. Generally, the incidence of MDR1/Pgp expression was higher in pretreated samples, and treatments with doxorubicin and/or vincristine were more effective in MDR1/Pgp expression than with alkylating agents. A significant association was observed between MDR1 /Pgp-positiveness and the ability of verapmil to increase doxorubicin sensitivity, suggesting functional relevance of MDR1/Pgp expression. MRP (multidrug resistance protein) expression was detected in 20.5% of 88 myeloma samples, in 26% at the mRNA level analyzed by quantitative reverse transriptase-polymerase chain reaction, and in only 3 of 79 samples by immunohistochemistry. LRP (lung-resistance protein) protein expression was observed in 12.5% of 72 myeloma samples. MRP and LRP expression was similar in samples with and without prior therapy. Approximately 80% of the myeloma samples with detectable mRNA expression of MDRI and MRP exhibited low expression levels corresponding to < 10% of the Pgp- and MRP-overexpressing multidrug-resistant human myeloma cell lines 8226/Dox6 and 8226/DOXint40c, respectively. Some normal bone marrow samples showed higher levels of MRP mRNA as compared to myeloma specimens, whereas MDRI mRNA expression in normal bone marrow was much lower (< or = 5%) than that in 8226/Dox6. These findings indicate a requirement to develop single-cell assays for MRP detection in multiple myeloma that are more sensitive than immunohistochemistry and might be useful to evaluate the incidence of genes associated with MDR.

KW - Antineoplastic Agents

KW - DNA, Complementary

KW - Doxorubicin

KW - Drug Resistance, Multiple

KW - Humans

KW - Multiple Myeloma

KW - Neoplasm Proteins

KW - P-Glycoprotein

KW - Reverse Transcriptase Polymerase Chain Reaction

KW - Tumor Cells, Cultured

KW - Vault Ribonucleoprotein Particles

KW - Verapamil

U2 - 10.1385/MO:19:2:87

DO - 10.1385/MO:19:2:87

M3 - SCORING: Journal article

C2 - 12180485

VL - 19

SP - 87

EP - 104

JO - MED ONCOL

JF - MED ONCOL

SN - 1357-0560

IS - 2

ER -