Expression pattern of long non-coding RNA growth arrest-specific 5 in the remission induction therapy in childhood acute lymphoblastic leukemia

Abstract

Summary 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.

The Non-Coding RNA GAS5 and Its Role in Tumor Therapy-Induced Resistance

“…GAS5 expression was recently found to be tightly linked to therapy progression in acute lymphoblastic leukemia (ALL) [ 30 ]. In the study of Gasic et al [ 30 ], GAS5 expression was reduced at day 33 of the induction therapy as compared to day 15, yet with still higher levels, compared to the time of diagnosis. This report suggested two interesting findings.…”

Is dynamic thiol/disulfide homeostasis associated with the prognosis of myelodysplastic syndrome?

“…The aging of hemato poietic cells, caused by both endogenic and exogenic cellular factors, disrupted hematopoietic environments, self-restoration, and regeneration, is related to immune system reconfiguration and the increase in leukemia incidence. Ghoti et al (14) reported oxidative stress in erythrocytes, thrombocytes, and polymorphonuclear leukocytes and increased serum ROS levels in low-risk MDS patients. In addition, in another study, it was shown that this oxidative situation is related to the significant increase in oxidative DNA damage in BM cells in MDS patients.…”

“…It is known that cancer cells adapt to oxidative conditions by elevating their antioxidant capacities, decreasing the ability to regulate other changes in oxidative stress compared to normal cells. The elevation of antioxidants as an adaptation to intracellular oxidative stress is a well-known phenomenon (14,15).…”

Pharmacogenomic and Pharmacotranscriptomic Profiling of Childhood Acute Lymphoblastic Leukemia: Paving the Way to Personalized Treatment

“…However, some results have been reported. The long noncoding RNA GAS5 was shown to be associated with a poor GCs response in childhood ALL during remission induction therapy [38]. GAS5 imitates the glucocorticoid response element (GRE) sequence, which is a DNA sequence to which the GC-GR complex needs to bind to in order to realize its effect, thus GAS5 can bind the GC-GR complex and stop it from binding to the GRE sequence [39].…”