P063 | Analysis of the expression profile of long non-codingRNAs in patients affected by T-cell large granular lymphocyte leukemia

Introduction. Large Granular Lymphocyte Leukemia (LGLL) is a rare chronic lymphoproliferative disorder, most commonly found in the T-cell form (T-LGLL). Activating STAT3 and STAT5B mutations are associated with symptomatic cytopenias in CD8+ T-LGLL and a milder course in CD4+ T-LGLL, respectively. The disease ranges from indolent to aggressive conditions, with low-dose immunosuppressive drugs often giving only transient responses, revealing the need for targeted therapies. With the goal of discovering potential diagnostic markers and therapeutic targets, this study investigates long non-coding RNAs (lncRNAs), including key regulators of gene expression and oncogenesis, a matter still unexplored in T-LGLL. Methods. For lncRNA identification and quantification, RNA-sequencing (RNA-seq) was performed on purified CD57+ LGLs from a pilot cohort of 20 T-LGLL patients, subdivided by immunophenotype (CD8+/CD4+) and mutational status (STAT3/STAT5B), and 5 healthy donors (HD). To test whether lncRNA changes in STAT3-mutated patients were dependent on JAK2/STAT3 activation, primary T-LGLs were stimulated with IL-6 (20 ng/mL) and treated with STATTIC (3.5 μM). Treatment efficacy was assessed by western blot to measure STAT3 phosphorylation and by RT-qPCR to evaluate lncRNA expression levels following treatment.Results. Transcriptome profiling identified 5,543 differentially expressed genes (p-adj