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Cited by 70Acute Lymphoblastic Leukemia researchT-cell and B-cell ImmunologyGenomics and Chromatin Dynamics

The T-ALL related gene BCL11B regulates the initial stages of human T-cell differentiation

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Ha, V L, Luong, A, Li, F, Casero, D, Malvar, J, Kim, Y M, Bhatia, R, Crooks, G M +1 more·2017·Leukemia
DOI 10.1038/leu.2017.70PMC PMC5599326
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Abstract

The initial stages of T-cell differentiation are characterized by a progressive commitment to the T-cell lineage, a process that involves the loss of alternative (myelo-erythroid, NK, B) lineage potentials. Aberrant differentiation during these stages can result in T-cell acute lymphoblastic leukemia (T-ALL). However, the mechanisms regulating the initial stages of human T-cell differentiation are obscure. Through loss of function studies, we showed BCL11B, a transcription factor recurrently mutated T-ALL, is essential for T-lineage commitment, particularly the repression of NK and myeloid potentials, and the induction of T-lineage genes, during the initial stages of human T-cell differentiation. In gain of function studies, BCL11B inhibited growth of and induced a T-lineage transcriptional program in T-ALL cells. We found previously unknown differentiation stage-specific DNA binding of BCL11B at multiple T-lineage genes; target genes showed BCL11B-dependent expression, suggesting a transcriptional activator role for BCL11B at these genes. Transcriptional analyses revealed differences in the regulatory actions of BCL11B between human and murine thymopoiesis. Our studies show BCL11B is a key regulator of the initial stages of human T-cell differentiation and delineate the BCL11B transcriptional program, enabling the dissection of the underpinnings of normal T-cell differentiation and providing a resource for understanding dysregulations in T-ALL.

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  • PU.1 expression timing relative to other developmentally regulated transcription factors is conserved between human and mouse.

    “This expression timing relative to other developmentally regulated transcription factors is conserved between human and mouse (35, 36)”

    From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [36]

    The Results section on BCL11B expression during human thymopoiesis describes when BCL11B appears in human progenitors, while the Discussion compares some BCL11B effects in humans and mice. Neither passage addresses PU.1 expression timing relative to other transcription factors across the two species; searches for PU.1 and SPI1 found no relevant passage. Page numbers were not available in our copy. (LLM, conf=0.72)

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Cited by

Sorted by citations

Authors
Ha, V. L., Luong, A., Li, F., Casero, D., Malvar, J., Kim, Y. M., Bhatia, R., Crooks, G. M., & Parekh, C.
Affiliations
  • Children's Hospital Los Angeles (US)
  • University of California, Los Angeles (US)
  • University of Southern California (US)
  • University of Alabama at Birmingham (US)
Corresponding author
Parekh, C
ORCID
Venue
Leukemia
Publisher
Springer Science and Business Media LLC
Published
2017-02-24
Volume
31
Issue
11
Pages
2503-2514
ISSN
  • 0887-6924 (ISSN-L)
  • 1476-5551
DOI
10.1038/leu.2017.70
PMC
PMC5599326
OpenAlex
W2590083701
Cited by
70
References
5
Citations by year
2026: 3 · 2025: 2 · 2024: 8 · 2023: 10 · 2022: 11 · 2021: 12 · 2020: 14 · 2019: 6 · 2018: 3 · 2017: 1
FWCI
6.16
Type
journal article
Language
en
Open access
Licence
Locations
  • Leukemia (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
Funders
  • National Institutes of Health (4k12hd034610-20)
  • National Heart, Lung, and Blood Institute (P01HL073104)
  • National Cancer Institute (R01CA172896, P30CA014089)
  • National Institute of Allergy and Infectious Diseases (P30AI028697)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (K12 HD-034610, K12HD052954)
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Acute Lymphoblastic Leukemia research
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
BCL11B, T-cell acute lymphoblastic leukemia, T cell differentiation, transcription factors, transcriptional regulation, thymopoiesis, DNA binding, transcriptional activator
MeSH terms
Cell Differentiation, Humans, Repressor Proteins, T-Lymphocytes, Tumor Suppressor Proteins, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

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