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

Abstract

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.

Keywords

B-cell lymphoma/leukemia 11A / Transcription factor / Gene regulation / Leukemia / Chromatin immunoprecipitation sequencing analyses

Funding

Support for this work was provided by the Lymphoma Research Foundation Fellowship 300463 (to J.D.D.), the NIH Grant R01CA31534, the Cancer Prevention Research Institute of Texas (CPRIT) Grants RP120348 and RP120459, and the Marie Betzner Morrow Centennial Endowment (to H.O.T.).

Conflict of interest

The authors declare no conflicts of interest.

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