SPECIAL SEMINAR - Dr Loélia BABIN - Centre de recherche de Cancérologie de TOULOUSE (CRCT) : "Circular RNA and pediatric lymphoma resistance" - Centre De Lutte Contre Le Cancer Eugène Marquis

Circular RNA and pediatric lymphoma resistance

Dr Loélia BABIN

Post-Doctoral Researcher

Cancer Research Center of Toulouse (CRCT)

Abstract
ALK(+) anaplastic large cell lymphoma is a rare pediatric lymphoma affecting mature T cells. It is mainly associated with the t(2;5) translocation leading to the NPM-ALK fusion protein expression. The first-line treatment is a chemotherapy with high response rate. Nonetheless, 30% of patients relapse early with a poor prognosis. In case of resistance, tyrosine kinase inhibitor (TKi) targeting ALK (crizotinib) can be used. Unfortunately, resistance to ALK TKi have also been observed. It is therefore necessary to better understand these resistance mechanisms in order to find new therapeutic targets and to identify predictive biomarkers. Recent studies have shown the importance of circular RNAs (circRNAs), a new class of noncoding RNAs, in tumor stage and treatment resistance. They are therefore robust and can be detected in body fluid, which makes them very good biomarkers. Using RNAseq analysis of ALK(+) primary biopsies, we identified several circular RNA dysregulated in ALK(+) ALCL. Thanks to original cellular models we showed that some of them are notably involved in treatment resistance and could be used as therapeutic targets or resistance biomarkers (Andraos et al, in review in Scientific report; Babin et al, in review in Leukemia, bioRxiv preprint doi: https://doi.org/10.64898/2026.01.13.699235) In long term perspectives, we hope to propose new therapeutical strategy for patients with crizotinib refractory disease whose chances of recovery are currently very slim.