Related Experiment Videos
Expression of breast cancer resistance protein in blast cells from patients with acute leukemia
1University of Maryland Greenebaum Cancer Center; the Department of Medicine, Division of Hematology/Oncology, University of Maryland School of Medicine, Baltimore, MD 21201, USA. dross@umgcc.umaryland.edu
Abstract:
Breast cancer resistance protein (BCRP) is a novel member of the adenosine triphosphate-binding cassette superfamily of transport proteins. Transfection and enforced expression of BCRP in drug-sensitive cells confer resistance to mitoxantrone, doxorubicin, daunorubicin, and topotecan. We studied blast cells from 21 acute leukemia patients (20 acute myeloid leukemia, 1 acute lymphocytic leukemia) for the expression of BCRP mRNA using a quantitative reverse-transcription polymerase chain reaction assay. BCRP mRNA expression varied more than 1000-fold among the samples tested, with low or barely detectable expression in half of the samples. Seven samples (33%) had relatively high expression of BCRP mRNA. High expression of BCRP did not correlate strongly with high expression of P-glycoprotein, suggesting that BCRP may cause resistance to certain antileukemic drugs in P-glycoprotein-negative cases. High expression of BCRP mRNA is sufficiently frequent in AML to warrant more extensive investigations to determine the relation of disease subtype and treatment outcome to BCRP expression and function.
Insights
Breast cancer resistance protein (BCRP) is frequently expressed in acute myeloid leukemia (AML) blast cells. High BCRP mRNA levels may contribute to drug resistance in leukemia patients, independent of P-glycoprotein.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Breast cancer resistance protein (BCRP) is an ATP-binding cassette transporter.
- BCRP confers resistance to various chemotherapy drugs, including mitoxantrone, doxorubicin, daunorubicin, and topotecan.
- BCRP's role in acute leukemia drug resistance is not fully understood.
Purpose of the Study:
- To investigate the expression levels of BCRP mRNA in acute leukemia blast cells.
- To determine the correlation between BCRP expression and P-glycoprotein expression.
- To assess the potential role of BCRP in mediating drug resistance in acute myeloid leukemia (AML).
Main Methods:
- Quantitative reverse-transcription polymerase chain reaction (RT-PCR) assay.
- Analysis of BCRP mRNA expression in blast cells from 21 acute leukemia patients (20 AML, 1 ALL).
- Comparison of BCRP expression with P-glycoprotein expression levels.
Main Results:
- BCRP mRNA expression varied over 1000-fold among patient samples.
- Half of the samples showed low or undetectable BCRP mRNA expression.
- Seven samples (33%) exhibited relatively high BCRP mRNA expression.
- High BCRP expression did not strongly correlate with high P-glycoprotein expression.
Conclusions:
- High BCRP mRNA expression is common in AML blast cells.
- BCRP may contribute to antileukemic drug resistance, particularly in P-glycoprotein-negative cases.
- Further research is warranted to explore the relationship between BCRP, disease subtype, and treatment outcomes in AML.