B-cell lymphoma/leukemia 11A transcriptional targets and chromatin binding patterns in human leukemias

B-cell lymphoma/leukemia 11A (BCL11A) is a zinc-finger transcription factor that plays a crucial role in B-cell development. It is highly expressed in numerous neoplasias, making it a potential risk factor for cancer. Recently, we identified a subset of plasmacytoid dendritic cells (pDC) in mice that are derived from common lymphoid progenitors, which primarily give rise to lymphocytes. We further demonstrated that transcription of B cell-derived pDC (B-pDC) genes in this murine subset is highly regulated by BCL11A. To investigate whether a similar lineage exists in humans, we identified direct BCL11A transcription targets and chromatin binding patterns shared between malignant human pDC and B-cell leukemias. We focused on cell lines such as NALM6 (pre-B leukemia), Raji (B-cell Burkitt’s lymphoma), and GM12878 (pre-B-cell leukemia) and compared BCL11A targets to those in the CAL-1 human pDC cell line. Our findings revealed that BCL11A bound to promoter regions of genes such as PAX5, TCF3, and ID3 in B-cell leukemias, while it exclusively bound AXL, SIGLEC1, and IGLL1 in CAL-1 human pDCs. These results suggest that an evolutionarily conserved transcriptional hierarchy underlies B-pDC commitment, distinguishing it in human leukemias.