T-cell large granular lymphocyte leukemia (T-LGLL) is characterized by a clonal expansion of cytotoxic CD8+ T-cells. The pathogenesis of LGLL is not fully understood, and with no FDA-approved therapies, there is a need for a deeper understanding of the disease's molecular complexities and impact on the tissue microenvironment. It has been shown that T-LGLL cells accumulate in patient tissues including bone marrow and spleen. We confirmed via IHC staining for T-cell markers (CD3, CD8) that T-LGLL cells cluster and form distinct linear arrays in intrasinusoidal spaces in patient tissues vs. healthy donors. In addition to these histopathological findings, we have generated single-cell RNA sequencing data from peripheral blood mononuclear cells from T-LGLL patients, which revealed the upregulation of genes related to cell adhesion pathways. To further quantify cell-cell communication networks, we used LIgand-receptor ANalysis frAmework (LIANA). These results were compared to healthy donors to identify shared and unique interactions between T-LGLL cells and normal counterpart CD8-TEMRA cells. Several genes related to cell adhesion pathways including PECAM and ANXA1 were uniquely expressed by T-LGLL cells. We hypothesize that the upregulation of these genes related to cell adhesion pathways and cell-cell interactions contribute to T-LGLL accumulation in tissues. Ongoing research will focus on spatial analysis of LGLL to gain deeper insights into the tissue microenvironment. This work aims to identify biomarkers, elucidate pathogenic mechanisms, and discover novel therapeutic targets to disrupt key pathways driving LGLL pathogenesis.
