AccScience Publishing / GPD / Online First / DOI: 10.36922/gpd.8131
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B-cell lymphoma/leukemia 11A transcriptional targets and chromatin binding patterns in human leukemias

Joseph D. Dekker1 ,  Alessandra M. Araujo1 ,  Haley O. Tucker1*
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1 Department of Molecular Biosciences, Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, Texas, United States of America
GPD, 8131 https://doi.org/10.36922/gpd.8131
Submitted: 23 December 2024 | Revised: 2 April 2025 | Accepted: 3 April 2025 | Published: 25 April 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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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.

Graphical abstract
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.
References
  1. Harman BC, Miller JP, Nikbakht N, Gerstein R, Allman D. Mouse plasmacytoid dendritic cells derive exclusively from estrogen-resistant myeloid progenitors. Blood. 2006;108(3):878-885. doi: 10.1182/blood-2005-11-4545

 

  1. Adams NM, Das A, Yun TJ, Reizis B. Ontogeny and function of plasmacytoid dendritic cells. Annu Rev Immunol. 2024;42(1):347-373. doi: 10.1146/annurev-immunol-090122-041105

 

  1. Reizis B, Bunin A, Ghosh HS, Lewis KL, Sisirak V. Plasmacytoid dendritic cells: Recent progress and open questions. Annu Rev Immunol. 2011;29:163-183. doi: 10.1146/annurev-immunol-031210-101345

 

  1. Shigematsu H, Reizis B, Iwasaki H, et al. Plasmacytoid dendritic cells activate lymphoid-specific genetic programs irrespective of their cellular origin. Immunity. 2004;21(1):43-53. doi: 10.1016/j.immuni.2004.06.011

 

  1. Wang YH, Liu YJ. Mysterious origin of plasmacytoid dendritic cell precursors. Immunity. 2004;21:1-2. doi: 10.1016/j.immuni.2004.07.003S107476130400175

 

  1. Pelayo R, Hirose J, Huang J, et al. Derivation of 2 categories of plasmacytoid dendritic cells in murine bone marrow. Blood. 2005;105(11):4407-4415. doi: 10.1182/blood-2004-07-2529

 

  1. Araujo AM, Dekker JD, Garrison K, et al. Lymphoid origin of intrinsically activated plasmacytoid dendritic cells in mice. Elife. 2024;13:RP96394. doi: 10.7554/eLife.96394

 

  1. Ippolito GC, Dekker JD, Wang YH, et al. Dendritic cell fate is determined by BCL11A. Proc Natl Acad Sci U S A. 2014;111(11):E998-E1006. doi: 10.1073/pnas.1319228111

 

  1. Feng J, Pucella JN, Jang G, et al. Clonal lineage tracing reveals shared origin of conventional and plasmacytoid dendritic cells. Immunity. 2022;55(3):405-422.e11. doi: 10.1016/j.immuni.2022.01.016

 

  1. Villani AC, Satija R, Reynolds G, et al. Single-cell RNA-seq reveals new types of human blood dendritic cells, monocytes, and progenitors. Science. 2017;356(6335):eaah4573. doi: 10.1126/science.aah4573

 

  1. Zhang H, Gregorio JD, Iwahori T, et al. A distinct subset of plasmacytoid dendritic cells induces activation and differentiation of B and T lymphocytes. Proc Natl Acad Sci U S A. 2017;114(8):1988-1993. doi: 10.1073/pnas.1610630114

 

  1. Alcántara-Hernández M, Leylek R, Wagar LE, et al. High- Dimensional phenotypic mapping of human dendritic cells reveals interindividual variation and tissue specialization. Immunity. 2017;47(6):1037-1050.e6. doi: 10.1016/j.immuni.2017.11.001

 

  1. Matsui T, Connolly JE, Michnevitz M, et al. CD2 distinguishes two subsets of human plasmacytoid dendritic cells with distinct phenotype and functions. J Immunol. 2009;182(11):6815-6823. doi: 10.4049/jimmunol.0802008

 

  1. Reizis B. Plasmacytoid dendritic cells: Development, regulation, and function. Immunity. 2019;50(1):37-50. doi: 10.1016/j.immuni.2018.12.027

 

  1. Liu P, Keller JR, Ortiz M, et al. Bcl11a is essential for normal lymphoid development. Nat Immunol. 2003;4(6):525-532. doi: 10.1038/ni925

 

  1. Yu Y, Wang J, Khaled W, et al. Bcl11a is essential for lymphoid development and negatively regulates p53. J Exp Med. 2012;209(13):2467-2483. doi: 10.1084/jem.20121846

 

  1. Shi H, Li C, Feng W, et al. BCL11A is oncogenic and predicts poor outcomes in natural killer/T-cell lymphoma. Front Pharmacol. 2020;11:820. doi: 10.3389/fphar.2020.00820

 

  1. Seachrist DD, Hannigan MM, Ingles NN, et al. The transcriptional repressor BCL11A promotes breast cancer metastasis. J Biol Chem. 2020;295(33):11707-11719. doi: 10.1074/jbc.RA120.014018

 

  1. Borrayo-LóPez FJ, Ibarra-Cortés B, Perea-Díaz F, et al. Foetal hemoglobin elevation, unfavorable prognosis, and protective role of genetic variants HBG2 rs7482144, HBS1L-MYB rs9399137 and BCL11A rs4671393 in children with ALL. J Genet. 2024;103:17.

 

  1. Sunami Y, Yokoyama T, Yoshino S, et al. BCL11A promotes myeloid leukemogenesis by repressing PU.1 target genes. Blood Adv. 2022;6(6):1827-1843. doi: 10.1182/bloodadvances.2021004558

 

  1. Satterwhite E, Sonoki T, Willis TG, et al. The BCL11 gene family: Involvement of BCL11A in lymphoid malignancies. Blood. 2001;98(12):3413-3420. doi: 10.1182/blood.v98.12.3413

 

  1. Benjamini Y, Hochberg Y. Controlling the false discovery rate: A practical and powerful approach to multiple testing. J R Stat Soc Series B (Methodol). 1995;57(1):289-300. doi: 10.1111/j.2517-6161.1995.tb02031.x

 

  1. Maeda T, Murata K, Fukushima T, et al. A novel plasmacytoid dendritic cell line, CAL-1, established from a patient with blastic natural killer cell lymphoma. Int J Hematol. 2005;81(2):148-154. doi: 10.1532/ijh97.04116

 

  1. Adachi N, So S, Iiizumi S, et al. The human pre-B cell line nalm-6 is highly proficient in gene targeting by homologous recombination. DNA Cell Biol. 2006;1:19-24. doi: 10.1089/dna.2006.25.19

 

  1. Drexler HG, Minowada J. History and classification of human leukemia-lymphoma cell lines. Leuk Lymphoma. 1998;31(3-4):305-316. doi: 10.3109/10428199809059223

 

  1. ENCODE Project Consortium. The Encode (ENCyclopedia of DNA Elements) Project. Science. 2004;306:636-640. doi: 10.1126/science.1105136

 

  1. Cisse B, Caton ML, Lehner M, et al. Transcription factorE2-2 is an essential and specific regulator of plasmacytoid dendritic cell development. Cell. 2008;135(1):37-48. doi: 10.1016/j.cell.2008.09.016

 

  1. Karrich JJ, Balzarolo M, Schmidlin H, et al. The transcription factor Spi-B regulates human plasmacytoid dendritic cell survival through direct induction of the antiapoptotic gene BCL2-A1. Blood. 2012;119(22):5191-5200. doi: 10.1182/blood-2011-07-370239

 

  1. Ceribelli M, Hou ZE, Kelly PN, et al. A druggable TCF4- and BRD4-dependent transcriptional network sustains malignancy in blastic plasmacytoid dendritic cell neoplasm. Cancer Cell. 2016;30(5):764-778. doi: 10.1016/j.ccell.2016.10.002

 

  1. Kamikubo Y. Genetic compensation of RUNX family transcription factors in leukemia. Cancer Sci. 2018;109(8):2358-2363. doi: 10.1111/cas.13664

 

  1. Caulier AL, Sankaran VG. Molecular and cellular mechanisms that regulate human erythropoiesis. Blood. 2022;139(16):2450-2459. doi: 10.1182/blood.2021011044

 

  1. Wang W, Xu J, Khoury JD, et al. Immunophenotypic and molecular features of acute myeloid leukemia with plasmacytoid dendritic cell differentiation are distinct from blastic plasmacytoid dendritic cell neoplasm. Cancers (Basel). 2022;14(14):3375. doi: 10.3390/cancers14143375

 

  1. Axelrod H, Pienta KJ. Axl as a mediator of cellular growth and survival. Oncotarget. 2014;5(19):8818-8852. doi: 10.18632/oncotarget.2422

 

  1. Ghosh HS, Cisse B, Bunin A, Lewis KL, Reizis B. Continuous expression of the transcription factor e2-2 maintains the cell fate of mature plasmacytoid dendritic cells. Immunity. 2010;33(6):905-916. doi: 10.1016/j.immuni.2010.11.023

 

  1. García-Aznar JM, Alvarez SA, Del Castillo TB. Pivotal role of BCL11B in the immune, hematopoietic and nervous systems: A review of the BCL11A-associated phenotypes from the genetic perspective. Genes Immun. 2024;25:232-241. doi: 10.1038/s41435-024-00263-w

 

  1. Engelsen AST, Lotsberg ML, Abou Khouzam R, et al. Dissecting the role of AXL in cancer immune escape and resistance to immune checkpoint inhibition. Front Immunol. 2022;13:869676. doi: 10.3389/fimmu.2022.869676

 

  1. Schmid ET, Pang IK, Carrera Silva EA, et al. AXL receptor tyrosine kinase is required for T cell priming and antiviral immunity. Elife. 2016;5:e12414. doi: 10.7554/eLife.12414

 

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Gene & Protein in Disease, Electronic ISSN: 2811-003X Published by AccScience Publishing
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