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Expression Pattern of Long Non-coding RNA Growth Arrest-specific 5 in the Remission Induction Therapy in Childhood
Vladimir Gasic1, Biljana Stankovic1, Branka Zukic1
1Laboratory for Molecular Biomedicine, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Background:
Long non-coding RNA growth arrest-specific 5 (GAS5) is deregulated in many cancers because of its role in cell growth arrest and apoptosis. Additionally, GAS5 interacts with glucocorticoid receptor, making it a potential pharmacotranscription marker of glucocorticoid (GC) therapy. In this study, we aimed at analysing GAS5 expression in the remission induction therapy phase of childhood acute lymphoblastic leukemia (ALL), in which GCs are mandatorily used, and to correlate it with therapy response.
Methods:
GAS5 expression was measured in peripheral blood mononuclear cells taken from 29 childhood ALL patients at diagnosis, on day 15 and day 33 of remission induction therapy using RT-qPCR methodology.
Results:
Our results have shown interindividual differences in GAS5 expression at all time points. For each ALL patient, GAS5 expression was higher on day 15 in comparison to its level at diagnosis (p<0.0005). On day 33, the level of GAS5 expression decreased in comparison with day 15 (p<0.0005), but it was still significantly higher than at diagnosis for the majority of patients (p=0.001). Patients whose number of blasts on day 8 was below 100 per μL of peripheral blood had a higher GAS5 expression at diagnosis (p=0.016), and lower ratio day 15/diagnosis (p=0.009).
Conclusions:
Our results suggest that the expression level of GAS5 could be a potential marker of therapy response in remission induction therapy of childhood ALL.
Insights
Long non-coding RNA GAS5 is a potential marker for therapy response in childhood acute lymphoblastic leukemia (ALL). Its expression levels change during remission induction therapy, correlating with treatment outcomes.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNA growth arrest-specific 5 (GAS5) is implicated in cancer cell growth and apoptosis.
- GAS5 interacts with the glucocorticoid receptor, suggesting its role as a pharmacotranscriptional marker for glucocorticoid (GC) therapy.
Purpose of the Study:
- To analyze GAS5 expression during remission induction therapy in childhood acute lymphoblastic leukemia (ALL).
- To correlate GAS5 expression levels with therapy response in pediatric ALL patients.
Main Methods:
- GAS5 expression was quantified using RT-qPCR in peripheral blood mononuclear cells.
- Samples were collected from 29 childhood ALL patients at diagnosis, day 15, and day 33 of remission induction therapy.
Main Results:
- Significant interindividual differences in GAS5 expression were observed across all time points.
- GAS5 expression increased from diagnosis to day 15 (p<0.0005) and decreased by day 33 (p<0.0005), remaining higher than at diagnosis (p=0.001).
- Higher diagnostic GAS5 expression (p=0.016) and a lower day 15/diagnosis ratio (p=0.009) were associated with favorable early blast reduction.
Conclusions:
- GAS5 expression levels show dynamic changes during remission induction therapy for childhood ALL.
- GAS5 may serve as a predictive biomarker for therapy response in pediatric ALL.
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