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Gene & Protein in Disease The roles and mechanisms of ETS1 in diseases

an ERK-dependent manner in all melanoma cell lines, increased in adult T-cell leukemia/lymphoma of North
that mutations in TRET create ETS transcription factor- American – descendent patient (NA-ATLL) cell lines and
binding sites, and that ETS1 binding to the mutated TRET primary tumor samples, and knocking down ETS1 in
promoter leads to re-expression of TRET . Furthermore, NA-ATLL cells resulted in cell growth inhibition, indicating
[67]
Gabler et al. reported that the coexistence of mutations in that ETS1 is a new dominant oncogenic transcription
[78]
serine/threonine kinase (BRAF V600E ) and TRET promoter regulator in NA-ATLL .
leads to cancer cell proliferation and immortalization, and
ETS1 functionally links these two driver alterations . 5. Conclusion
[71]
These studies provide significant insights into the roles of This comprehensive review provides an in-depth
ETS1 in regulating the immortalization of cancer cells by examination of the outcomes and functions associated
the mutated TRET promoter, which could contribute to with ETS1. The myriad roles of this transcription factor
immense therapeutic implications. assume in immune-related diseases that are reviewed.

4.6. The role of ETS1 in B-cell and T-cell malignancies Furthermore, this review explores the diverse contributions
of ETS1 to the onset and progression of various diseases,
ETS1 has crucial roles in the development of lymphoid incorporating the most recent findings from scientific
tissue and the activation of lymphocytes, indicating research. ETS1 not only induces immune-related diseases
that it has a potential relationship with B-cell and T-cell but also correlates with disease severity. Although these
malignancies. A previous study focused on the multiple studies provide us with a clear understanding of the role
roles and regulatory mechanisms of ETS1 in hematological of ETS1 in immune-related diseases, additional specific
development, including T-cell and natural killer (NK) cell molecular mechanisms have not been elucidated. We
activation and B-cell maturation and differentiation [72,73] . believe that the continuous development of research
With in-depth research on the mechanisms of action methods and technologies can enable further exploration
of ETS1 in diseases, its role as a key transcription factor of the diverse and complex roles of ETS1 in immune-
in B-cell and T-cell malignancies has gradually been related diseases, which may have significant implications
revealed. In classical Hodgkin’s lymphoma (cHL), for clinical treatment.
ETS1 is hypermethylated exclusively and is markedly
decreased in the cHL cell line. Recurrent deletions and Acknowledgments
loss of ETS1 expression could contribute to the potential None.
escape and survival of Hodgkin and Reed-Sternberg cells
(HRS) and impair B-cell development . In diffuse large Funding
[74]
B-cell lymphoma (DLBCL), 11q24.3 genomic lesions are
correlated with high expression levels of ETS1 and FLI1, This work was supported by the National Natural Science
and overexpression of these two genes could contribute Foundation of China (32060177, 82260397, and 82360328),
to the pathogenesis of DLBCL in a cooperative manner the Joint Special Fund of the Department of Science
and Technology, Yunnan Province – Kunming Medical
by deregulating genes involved in the germinal center
expression program and cell proliferation . Further University (202201AY070001-046 and 202301AY070001-
[75]
study of DLBCL demonstrated that ETS1 silencing 139), the Yunnan Fundamental Research Projects
affected genes involved in B-cell signaling, differentiation, (202201AT070292 and 202201AU070202), and the
cell cycle, and immune processes, highlighting its role Fund of Beijing Key Laboratory for HIV/AIDS Research
in lymphomagenesis, particularly in activated-like (BJYAHKF2021001).
B-cell (ABC) DLBCL . Recent research has indicated Conflict of interest
[73]
that B-cell receptor-mediated ETS1 phosphorylation
at threonine 38 is important for the growth of DLBCL The authors have no personal, financial, or institutional
cells and is related to the ABC-DLBCL phenotype but interest with regard to any of the drugs, materials, or
is predictive of poor outcome in patients with germinal devices described in this article.
center B-cell-like (GCB) DLBCL . Drug-mediated Author contributions
[76]
inhibition of ETS1 phosphorylation could have a positive
effect on lymphoma patients . Regarding the role of Conceptualization: Yi-Qun Kuang
[76]
ETS1 in T-cell malignancies, a recent study showed that Writing – original draft: Kai-Cheng Gao, Yu Zhao, Jie Jia,
Notch activation is closely related to the induction of T-cell Dan Liang, Lin Xu
acute lymphoblastic leukemia . Moreover, Luchtel et al. Writing – review and editing: Kai-Cheng Gao, Yu Zhao, Jie
[77]
reported that the expression of ETS1 was significantly Jia

Volume 2 Issue 4 (2023) 6 https://doi.org/10.36922/gpd.2141