IkBz target genes in chronic lymphocytic leukemia

However, the transcriptional and epigenetic programs regulated by IkBz in both normal and malignant B-cells remain poorly described. Here, we analyzed CLL cells by epigenomic profiling to dissect the molecular function of IkBz in leukemia.

In primary human B-cells and CLL samples, ChIP-seq and CUT&Tag analyses delineated a comprehensive genome-wide landscape of IkBz binding sites. Key genes, including NFKB2, BATF and FOXP1 gained IkBz binding after TLR stimulation in both CLL and B-cells, whereas CXCR5 was mainly bound in CLL cells. Pharmacological or genetic inhibition of IkBz signaling disrupted the induction of these molecules highlighting its potential role as a central transcriptional tuner that integrates TLR-mediated inflammatory pathways with BCR signaling and migration.