P002 | Multi-omics analysis unravels new biomarkers of relapse risk in adult Philadelphia-positive B-ALL

Introduction. The management and long-term outcome of adults with Philadelphia-positive Acute Lymphoblastic Leukemia (Ph+ B-ALL) improved since the introduction of tyrosine-kinase inhibitors (TKIs). With the administration of a chemo-free strategy combining second or third generation TKIs with Blinatumomab, hematological relapses occur in about 10% of cases (Foà. et al, 2024, Kantarjian et al, 2024). Nevertheless, mechanisms underlying relapse in Ph+ B-ALL still need to be clarified. In this context, the study of circular RNAs (circRNAs), single-stranded closed RNAs, adds a new layer to leukemic cells deciphering. In this study, we obtained a multi-omics characterization of Ph+ B-ALL using integrative data analysis to extract the molecular feature linked to an increased risk of relapse.Methods. Total RNA sequencing (RNA-seq) was performed on 17 diagnostic samples of Ph+ B-ALL patients (phase III GIMEMA ALL2820 trial), 10 without relapses (NR) and 7 who experienced a relapse (R). Genes and circRNA expression were quantified using CirComPara2. Differential expression (DE) analysis was done using DESeq2 (Adj.p-