Page 141 - GPD-4-2

Gene & Protein in Disease

SHORT COMMUNICATION
B-cell lymphoma/leukemia 11A transcriptional

targets and chromatin binding patterns in
human leukemias

Joseph D. Dekker † , Alessandra M. Araujo † , and Haley O. Tucker*

Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of
Texas at Austin, Austin, Texas, United States of America

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
† These authors contributed equally as NALM6 (pre-B leukemia), Raji (B-cell Burkitt’s lymphoma), and GM12878 (pre-B-
to this work. cell leukemia) and compared BCL11A targets to those in the CAL-1 human pDC cell
*Corresponding author: line. Our findings revealed that BCL11A bound to promoter regions of genes such as
Haley O. Tucker PAX5, TCF3, and ID3 in B-cell leukemias, while it exclusively bound AXL, SIGLEC1, and
(haleytucker@austin.utexas.edu) IGLL1 in CAL-1 human pDCs. These results suggest that an evolutionarily conserved
Citation: Dekker JD, Araujo AM, transcriptional hierarchy underlies B-pDC commitment, distinguishing it in human
Tucker HO. B-cell lymphoma/ leukemias.
leukemia 11A transcriptional targets
and chromatin binding patterns in
human leukemias. Gene Protein
Dis. 2025;4(2):8131. Keywords: B-cell lymphoma/leukemia 11A; Transcription factor; Gene regulation;
doi: 10.36922/gpd.8131 Leukemia; Chromatin immunoprecipitation sequencing analyses
Received: December 23, 2024
Revised: April 2, 2025
Accepted: April 3, 2025 1. Introduction
Published online: April 25, 2025 Plasmacytoid dendritic cells (pDCs) were first characterized as a lineage derived from
myeloid progenitors. However, subsequent studies in both humans and mice raised
1,2
Copyright: © 2025 Author(s).
3-6
This is an Open-Access article questions about the true lineage affiliation of pDCs. To address this issue, we previously
distributed under the terms of the employed B-cell-specific mb1(Cd79a/Igα)-driven Cre-mediated deletion in Rosa26-
Creative Commons Attribution yellow fluorescent protein mice, which led to the identification of pDCs derived from
License, permitting distribution,
7,8
and reproduction in any medium, common lymphoid progenitors (CLPs). These pDC-like B lymphoid cells (B-pDCs)
provided the original work is exhibited intrinsic activation, homed to secondary lymphoid organs, and, on expansion,
properly cited. promoted robust T-cell proliferation following toll-like receptor 9 engagement. Further
7
9
Publisher’s Note: AccScience supporting this concept, Feng et al. used a clonal lineage tracing strategy in mice and
Publishing remains neutral with demonstrated a shared, FMS-like tyrosine kinase 3-dependent pathway for pDCs and
regard to jurisdictional claims in
published maps and institutional B cells, originating from a shared CD81hi progenitor. Although B-pDCs do not secrete
affiliations. interferon-alpha, they express a unique profile of cytokines and exhibit high expression
Volume 4 Issue 2 (2025) 1 doi: 10.36922/gpd.8131