HSP and CD279 gene expression as candidate biomarkers in symptomatic LGLL patients

The clinical presentation of T-cell large granular lymphocytic leukemia (T-LGLL) is extremely variable: 30% of patients have neutropenia with no associated symptoms, others present with bacterial infections and sepsis may occur. Tools to predict patient outcome are lacking. Stemming from preliminary results obtained by single cell-RNAseq we investigated by qPCR HSP and IFIT gene families in 27 LGLL patients (23T-LGLL and 4 NK-LGLL), including 11 with neutropenia and/or thrombocytopenia and 16 asymptomatic for the disease. HSP90AA1 and HSPA1B, among HSP family and CD279 exhibited a significantly higher expression in CD3 + CD57 + sorted cells of symptomatic LGLL patients compared to asymptomatic patients and healthy controls. Also, monocytes derived from symptomatic LGLL patients expressed high levels of CCL3, CCL4 and CCL5 mRNA and of IL-1β, IL-6, TNF, and PD-L1 mRNA, thus confirming a pro-inflammatory cytokine profile reminiscent of a non-classical phenotype. Overall, these data provide a rationale for considering HSP and CD279 genes as potential biomarkers for distinguishing symptomatic LGLL patients from asymptomatic ones, emphasizing the importance of further research to explore their implications for targeted therapy development.