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.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -