Transcriptome analysis comparing PLCG2 WT and Mut REC-1 cells
Bruton tyrosine kinase inhibitors (BTKi) are successful in treatment of chronic lymphocytic leukemia (CLL), yet acquired resistance remains a challenge. In this study, REC-1 cell line that acquired resistance to BTKi tirabrutinib by long-term treatment gained a splice-site mutation (SSM) c.2236-1 G>T in PLCG2.  It resulted in the exon-skipped variant, ?21, which exhibited enhanced phospholipase activity. To further explore the differences on transcriptomic profiles, we performed RNA sequencing on WT, SSM, and L845F REC-1 cells. Gene set enrichment analysis identified multiple upregulated pathways such as NF-?B signaling and oxidative phosphorylation. The observed pathway deregulations may be linked to the presence of the activating PLCG2 mutations in these cells.
Bruton tyrosine kinase inhibitors (BTKi) are successful in treatment of chronic lymphocytic leukemia (CLL), yet acquired resistance remains a challenge. In this study, REC-1 cell line that acquired resistance to BTKi tirabrutinib by long-term treatment gained a splice-site mutation (SSM) c.2236-1 G>T in PLCG2.  It resulted in the exon-skipped variant, ?21, which exhibited enhanced phospholipase activity. To further explore the differences on transcriptomic profiles, we performed RNA sequencing on WT, SSM, and L845F REC-1 cells. Gene set enrichment analysis identified multiple upregulated pathways such as NF-?B signaling and oxidative phosphorylation. The observed pathway deregulations may be linked to the presence of the activating PLCG2 mutations in these cells.
University of Ulm