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Prognostic significance of adenosine deaminase in children with malignancies
M Hatzistilianou1, F Athanassiadou, D Catriu
12nd Department of Paediatrics, Aristotle University of Thessaloniki, Greece.
Insights
Adenosine deaminase (ADA) enzyme activity in children with acute lymphoblastic leukemia (ALL) and solid tumors varied significantly with disease stage. ADA levels were highest at disease onset and relapse in ALL patients, suggesting its potential as a biomarker.
Area of Science:
- Biochemistry
- Pediatric Oncology
- Enzymology
Background:
- Adenosine deaminase (ADA) is a key enzyme in purine metabolism.
- Altered enzyme activity can indicate underlying disease states, particularly in pediatric malignancies.
- Understanding ADA phenotype and activity may offer insights into disease biology.
Purpose of the Study:
- To investigate adenosine deaminase (ADA) phenotype and plasma enzyme activity in children with acute lymphoblastic leukemia (ALL) and solid tumors.
- To correlate ADA activity with disease status (onset, remission, therapy, relapse) and subtypes.
- To explore ADA as a potential biomarker and therapeutic target in pediatric cancers.
Main Methods:
- Erythrocyte ADA phenotype determination using cellulose acetate electrophoresis.
- Plasma ADA enzyme activity measurement via spectrophotometry.
- Comparative analysis of enzyme activity across disease groups, stages, and controls.
Main Results:
- All children exhibited the ADA1-1 phenotype.
- ADA activity was significantly elevated at disease onset and relapse in ALL patients compared to controls.
- ADA activity decreased during remission and near control levels at therapy completion in ALL.
- Children with solid tumors showed altered ADA activity profiles during different therapeutic stages.
Conclusions:
- ADA enzyme activity exhibits distinct patterns in pediatric acute lymphoblastic leukemia and solid tumors, varying with disease progression and treatment.
- The ADA1-1 phenotype is consistent across these pediatric malignancies.
- ADA activity may serve as a sensitive indicator for disease status and a potential target for novel chemotherapies.
Abstract:
In 33 children, 23 with acute lymphoblastic leukemia (ALL) and 10 with solid tumors, the phenotype of the enzyme adenosine deaminase (ADA) was detected in the erythrocytes by electrophoresis in cellulose acetate. In all children the ADA enzyme activity was also determined in the plasma by spectrophotometry at the onset of the disease, during remission, at the end of the therapy, and during relapse. The phenotype in all children was ADA1-1. There was a difference in enzyme activity between the mean values of children with ALI and those with solid tumors. There were also differences among the subtypes of ALL and also among the stages of ALL and the stages of solid tumors. In 23 children with ALL the mean value (MV) and the corresponding standard error (SEM) of enzyme activity at the onset of the disease were MV +/- SEM = 60.2 +/- 6.2 IU/L. This was higher than that of the control group (control group: MV +/- SEM = 27.8 +/- 3.3 IU/L). During remission the enzyme activity was lower than that of the control group (MV +/- SEM = 19.6 +/- 1.7 IU/L); at the end of the therapy it was MV +/- SEM = 24.0 +/- 1.3 IU/L, which is close to that of the control group; and during relapse it was much higher compared with the control group (MV +/- SEM = 73.1 +/- 4.6 IU/L). These values are discussed in connection to the leukaemic subtypes. In 10 children with solid tumors the mean value of enzyme activity at the onset of the disease was MV +/- SEM = 48.8 +/- 2.4 IU/L. During therapy it was MV +/- SEM = 32.4 +/- 1.9 IU/L and at the end of therapy MV +/- SEM = 22.1 +/- 2.5 IU/L. The aim of this work is to study the qualitative isoenzyme abnormalities to better understand the biological nature of the malignancies, to distinguish main groups and subsets of ALL and solid tumors on an enzymatic basis, and to identify possible sensitive key enzymes as targets for chemotherapy.