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P-glycoprotein and glutathione S-transferase pi in childhood acute lymphoblastic leukaemia
1University of Jena, Children's Hospital, Germany.
Insights
P-glycoprotein (P-170) expression in childhood acute lymphoblastic leukemia (ALL) is linked to a poorer prognosis. Increased glutathione S-transferase pi (GST-pi) also correlates with higher relapse rates in these patients.
Area of Science:
- Pediatric Oncology
- Hematology
- Cancer Biology
Background:
- Acute lymphoblastic leukemia (ALL) is the most common childhood cancer.
- Drug resistance mechanisms, including P-glycoprotein (P-170) and glutathione S-transferase pi (GST-pi), are critical factors in ALL treatment outcomes.
- Understanding the role of these resistance proteins in pediatric ALL is essential for improving patient prognosis.
Purpose of the Study:
- To investigate the expression of P-glycoprotein (P-170) and glutathione S-transferase pi (GST-pi) in pediatric ALL blast cells.
- To determine the correlation between the expression of these resistance proteins and clinical outcomes, including remission rates and relapse.
- To evaluate P-170 and GST-pi as prognostic factors in childhood ALL.
Main Methods:
- Immunohistochemistry was used to analyze P-170 and GST-pi expression in blast cells from 104 children with untreated ALL.
- Statistical analysis was performed to correlate protein expression with remission status, relapse rates, and other clinical factors.
- Multivariate analysis was conducted to identify independent prognostic factors.
Main Results:
- P-170 expression was detected in 35% of patients, and increased GST-pi in 50%.
- Coexpression of both proteins was found in 21% of cases.
- P-170-positive leukemia was associated with a significantly lower probability of remaining in first complete remission (P < 0.05).
- Overexpression of GST-pi correlated with a higher relapse rate (P = 0.001) and lower probability of first complete remission (P = 0.01).
Conclusions:
- P-glycoprotein (P-170) expression is an unfavorable prognostic factor in childhood acute lymphoblastic leukemia.
- Glutathione S-transferase pi (GST-pi) overexpression is also associated with poorer outcomes, including increased relapse rates.
- These resistance proteins are independent of common prognostic factors like sex, FAB type, and initial blast count.
Abstract:
Blast cells obtained from 104 children with untreated acute lymphoblastic leukaemia were analysed for the expression of P-glycoprotein (P-170) and glutathione S-transfer pi (GST-pi) using immunohistochemistry. Expression of P-170 was detected in 36 of 104 patients (35%) and increased GST-pi was seen in 52 patients (50%). Coexpression of both resistance proteins was observed in 22 leukaemias (21%), whereas no evidence of the resistance markers was found in 38 cases (37%). In patients with P-170-positive leukaemic cells, a significantly lower probability of remaining in first continuous complete remission (CCR) was observed when compared with patients with P-170-negative tumours (P < 0.05). However, only a trend for a more frequent expression of P-170 was found in the leukaemic cells of patients who experienced relapses (P = 0.099). Overexpression of GST-pi was correlated with a higher relapse rate (P = 0.001) and a lower probability of remaining in first CCR (P = 0.01). Expression of P-170 and GST-pi was independent of sex, FAB type, immunological subtype and initial blast cell count. The multivariate analysis indicated that only the expression of P-170 is an unfavourable prognostic factor for children with acute lymphoblastic leukaemia in addition to the prognostic clinical factors.