Childhood lymphomas: advanced - 30 juin 2021
In children under 15, lymphomas are the third leading cause of cancer in children after leukemia and brain tumors. Eva pour la vie provided € 50,000 in aid to the team of Dr Fabienne Meggetto (INSERM / CRCT) in Toulouse to better understand the most aggressive of them. The results and prospects are encouraging.
Summary of work and results, by Dr Fabienne Meggetto
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Lymphoma is cancer that affects cells of the immune system, i.e. lymphocytes. Lymphoma falls into two broad categories: Hodgkin lymphoma and non-Hodgkin lymphoma. In children under 15, the most common type of lymphoma is non-Hodgkin's. These are the 3rd cause of cancer in children after leukemia and brain tumors.
Anaplastic large cell lymphoma are aggressive peripheral non-Hodgkin's (apart from the thymus) that affects T lymphocytes. more frequent.
In children, 90% of anaplastic large cell lymphomas are associated with a chromosomal translocation which results in the expression of an abnormal protein, NPM-ALK. The standard treatment for pediatric anaplastic lymphomas is multidrug therapy. Although these T lymphomas are relatively sensitive to chemotherapy, about 30% of young patients relapse early and these relapses still have a poor prognosis. The search for biomarkers of early relapses is therefore essential for this pediatric cancer. Our main objective is therefore to identify biomarkers associated with failure / resistance to treatment of pediatric anaplastic large cell lymphomas associated with the oncogene NPM-ALKt.
Thanks to the funding obtained from the association Eva Pour la vie, we carried out, for the first time, the deep sequencing of all the RNAs (coding and non-coding including circRNAs) of 20 patients resistant and 20 patients sensitive to chemotherapy. . Bioinformatics analyzes of these data allowed us to identify a circular non-coding RNA signature associated with chemoresistance of ALK (+) LAGCs. Some of them are derived from the NPM-ALK translocation and are therefore specific for tumor cells.
Minimally invasive liquid biopsies are associated with easier and more frequent assessments with less morbidity compared to conventional biopsies . There is therefore a growing trend to explore the use of circulating biomarkers suitable for liquid biopsy. Circular RNAs are very stable biomarkers that can be efficiently detected in body fluids or in circulating cells, to allow early diagnosis, appropriate therapy selection, accurate prognosis and frequent therapeutic monitoring of cancers.
Our objective is now to determine whether the circular RNAs that we have identified can be used through a blood test as prognostic / predictive biomarkers of resistance to treatment of anaplastic NPM-ALK (+) lymphomas in children.