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P-Glycoprotein Expression in Drug-Resistant Chronic Lymphoproliferative Disorder
1a Division of Haematology, United Medical and Dental School of Guy's and St Thomas', St Thomas' Campus, London, England.
Insights
P-glycoprotein (P-gp) expression was studied in drug-resistant chronic lymphoproliferative disorders. P-gp was found in Adult T-cell leukemia/lymphoma and some prolymphocytic leukemia and chronic lymphocytic leukemia patients, suggesting a role in multidrug resistance.
Area of Science:
- Hematology
- Oncology
- Molecular Biology
Background:
- Chronic lymphoproliferative disorders (LPD) often exhibit drug resistance.
- P-glycoprotein (P-gp) is a key mediator of multidrug resistance (MDR) in cancer cells.
- Understanding P-gp expression in LPD is crucial for developing effective treatment strategies.
Purpose of the Study:
- To investigate the expression of P-glycoprotein (P-gp) in peripheral blood lymphocytes of patients with drug-resistant chronic lymphoproliferative disorders (LPD).
- To determine the potential role of P-gp in mediating multidrug resistance in various subtypes of LPD.
Main Methods:
- Direct immunofluorescence (IF) testing using monoclonal antibody (MoAb) C219 was employed.
- Peripheral blood lymphocytes from 60 patients with drug-resistant LPD were analyzed.
- Specific LPD subtypes included prolymphocytic leukemia (PLL), Adult T-cell leukemia/lymphoma (ATLL), hairy cell leukemia (HCL), and chronic lymphocytic leukemia (CLL).
Main Results:
- P-gp expression was detected in 4/15 PLL patients and both ATLL patients.
- None of the HCL patients expressed P-gp.
- P-gp was found in 2/14 anthracycline-resistant CLL patients, but not in CLL patients resistant only to chlorambucil.
- P-gp expression levels varied significantly (20-100%) among positive cases.
- PMA stimulation did not induce P-gp in non-resistant CLL lymphocytes.
Conclusions:
- Multidrug resistance in ATLL is likely mediated by P-gp over-expression.
- P-gp may also play a significant role in multidrug resistance in a subset of PLL and CLL patients.
- These findings highlight P-gp as a potential therapeutic target in specific drug-resistant lymphoproliferative disorders.
Abstract:
Peripheral blood lymphocytes from 60 patients with drug-resistant chronic lymphoproliferative disorders (LPD) were examined for expression of P-glycoprotein (P-gp) by direct immunofluorescence (IF) test using monoclonal antibody (MoAb) C219. Four of the 15 patients with prolymphocytic leukaemia (PLL), and both patients with Adult T cell leukaemialymphoma (ATLL) expressed P-gp. However, none of the 3 hairy cell leukaemia (HCL) patients expressed P-gp. Two of the 14 patients with anthracycline resistant chronic lymphocytic leukaemia (CLL) expressed P-gp but none of the 26 CLL patients resistant only to chlorambucil expressed it. The percentage of cells expressing P-gp varied considerably between different groups as well as different individuals (20-100%). Activation of peripheral blood lymphocytes from non-resistant CLL patients with phorbol myristic acetate (PMA) did not induce P-gp expression. It appears that multidrug resistance in ATLL is most likely mediated by over-expression of P-gp and this may also be an important mechanism in multidrug resistance in some PLL and CLL patients.
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