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P-glycoprotein activity predicts outcome in childhood acute lymphoblastic leukemia
Jacek Brozek1, Ewa Bryl, Anna Płoszyńska
1Departments of Pathophysiology, Medical University of Gdańsk, Gdańsk, Poland.
Insights
P-glycoprotein (P-gp) activity in childhood acute lymphoblastic leukemia (ALL) blasts is linked to poorer treatment outcomes. Children with P-gp positive blasts have significantly reduced overall survival, indicating its role as an independent prognostic factor.
Area of Science:
- Pediatric Oncology
- Molecular Biology
- Pharmacology
Background:
- Treatment of acute lymphoblastic leukemia (ALL) in children relies on cytostatics that are substrates of P-glycoprotein (P-gp).
- P-gp expression and function in leukemia cells can influence treatment efficacy and patient outcomes.
- Assessing P-gp function may offer prognostic value in pediatric ALL.
Purpose of the Study:
- To evaluate P-glycoprotein (P-gp) function in pediatric acute lymphoblastic leukemia (ALL) blast cells.
- To determine if P-gp function serves as a prognostic factor for overall survival in childhood ALL.
- To investigate the influence of P-gp activity on treatment response, including remission rates and steroid sensitivity.
Main Methods:
- P-gp function was assessed in blast cells using the verapamil-sensitive Rhodamine efflux assay.
- Rhodamine efflux was measured in cell samples from 45 children with ALL.
- Clinical characteristics and initial laboratory parameters were analyzed for associations with P-gp presence.
Main Results:
- P-gp function was detected in 16% (7 of 45) of pediatric ALL patients.
- No correlation was found between P-gp presence and clinical factors (age, sex, organomegaly) or initial laboratory parameters (immunophenotype, WBC, LDH).
- P-gp activity negatively impacted remission rates at day 33 and steroid therapy susceptibility.
- Children with P-gp positive blasts had a significantly lower 5-year overall survival (35%) compared to those negative for P-gp function (74%).
Conclusions:
- P-glycoprotein (P-gp) activity in pediatric acute lymphoblastic leukemia (ALL) blast cells is an independent negative prognostic factor.
- The presence of P-gp function is associated with poorer treatment outcomes and reduced overall survival.
- These findings suggest that P-gp functional assessment could aid in risk stratification for childhood ALL.
Abstract:
Treatment of children with acute lymphoblastic leukemia (ALL) is based on P-glycoprotein (P-gp)-dependent cytostatics. We assessed the P-gp function in blast cells as a possible prognostic factor and its influence on the overall survival. P-gp function was measured using the verapamil-sensitive Rhodamine efflux. Cell samples from 7 of 45 (16%) patients revealed rhodamine-efflux positive blasts. There were no relations between the presence of P-gp, clinical characteristics (age, sex, hepatomegaly, and splenomegaly) and initial laboratory parameters (immunophenotype, white blood cells count, and serum lactate dehydrogenase) in ALL. P-gp activity plays a negative role, both for a remission achieved on day 33 and for susceptibility to steroid therapy. Children bearing rhodamine-efflux positive blasts had a significantly shorter 5-year overall survival of 35%, as compared with 74% in those negative for P-gp function. Lack of any association with clinical characteristic and initial laboratory parameters suggests that presence of P-gp is an independent prognostic factor.
