Related Experiment Videos
Multiple drug resistance mediated by P-glycoprotein is not a major factor in a slow response to therapy in childhood
J Kanerva1, M Tiirikainen, A Mäkipernaa
1Children's Hospital, University of Helsinki, Finland. jukka.kanerva@helsinki.fi
Insights
P-glycoprotein (P-gp) mediated drug resistance is common in childhood acute lymphoblastic leukemia (ALL). However, this study found no link between P-gp expression and early treatment response in ALL patients.
Area of Science:
- Pediatric Oncology
- Hematology
- Molecular Biology
Background:
- Early treatment response in childhood acute lymphoblastic leukemia (ALL) is a key prognostic indicator.
- Drug resistance significantly contributes to poor outcomes in ALL.
- P-glycoprotein (P-gp)-mediated multiple drug resistance (MDR) is a widely studied resistance mechanism.
Purpose of the Study:
- To investigate the role of P-glycoprotein (P-gp) expression in childhood acute lymphoblastic leukemia (ALL).
- To determine the correlation between P-gp expression and early treatment response in ALL patients.
- To assess P-gp levels at diagnosis and relapse in pediatric ALL.
Main Methods:
- Flow cytometry using the monoclonal antibody JSB1 was employed to analyze P-gp expression.
- Bone marrow aspirate slides were reviewed to assess early treatment response.
- The study included 118 children with ALL, with samples collected at diagnosis (n=103) and relapse (n=15).
Main Results:
- Increased P-gp expression was observed in 53% of patients at diagnosis and 73% at relapse.
- No significant correlation was found between P-gp expression levels and early treatment response.
- Patients with T-cell ALL (T-ALL) exhibited significantly higher P-gp levels compared to other ALL subtypes (5.3% vs 1.0%, P = .002).
Conclusions:
- P-glycoprotein (P-gp)-mediated multiple drug resistance (MDR) is prevalent in childhood acute lymphoblastic leukemia (ALL), particularly at relapse.
- P-gp expression does not appear to be a determining factor for slow early response to ALL induction therapy.
- T-ALL is associated with higher P-gp expression, suggesting a potential role in specific ALL subtypes.
Abstract:
In childhood acute lymphoblastic leukemia (ALL), early response to treatment is an important prognostic factor and drug resistance is a major cause of poor outcome. One of the most investigated resistance mechanisms is P-glycoprotein (P-gp)-mediated multiple drug resistance (MDR). We analyzed P-gp using flow cytometry with monoclonal antibody JSB1 in a series of 118 children with ALL, 103 at diagnosis and 15 at relapse. Increased P-gp expression was found in 55 (53%) patients at diagnosis and in 11 (73%) at relapse. We also analyzed the bone marrow aspirate slides for early response to treatment in a central review. No correlation was found between P-gp and early response. Patients with T-ALL had higher P-gp levels than the others, 5.3% versus 1.0% (P = .002). We conclude that P-gp-mediated multiple drug resistance is not a factor in a slow response to ALL induction therapy.