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Current insights into the role of Fli-1 in hematopoiesis and malignant transformation

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Abstract

Fli-1, a member of the ETS family of transcription factors, was discovered in 1991 through retroviral insertional mutagenesis as a driver of mouse erythroleukemias. In the past 30 years, nearly 2000 papers have defined its biology and impact on normal development and cancer. In the hematopoietic system, Fli-1 controls self-renewal of stem cells and their differentiation into diverse mature blood cells. Fli-1 also controls endothelial survival and vasculogenesis, and high and low levels of Fli-1 are implicated in the auto-immune diseases systemic lupus erythematosus and systemic sclerosis, respectively. In addition, aberrant Fli-1 expression is observed in, and is essential for, the growth of multiple hematological malignancies and solid cancers. Here, we review the historical context and latest research on Fli-1, focusing on its role in hematopoiesis, immune response, and malignant transformation. The importance of identifying Fli-1 modulators (both agonists and antagonists) and their potential clinical applications is discussed.

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Abbreviations

F-MuLV:

Friend murine leukemia virus

SFFV:

Spleen focus forming virus

FV:

Friend virus

Fli-1:

Friend virus leukemia integration 1

TF:

Transcription factor

ETS:

E26 transformation-specific

ATA:

Amino-terminal transactivation

CTA:

Carboxy-terminal transactivation

HSCs:

Hematopoietic stem cells

TME:

Tumor microenvironment

hESCs:

Human embryonic stem cells

TCGA:

The cancer genome atlas

MEP:

Megakaryocyte erythroid progenitors

TPO:

Thrombopoietin

EPO:

Erythropoietin

TPA:

Tetradecanoylphorbol-13-acetate

LDBI:

LIM domain-binding protein 1

ChIp:

Chromatin immunoprecipitation

WAS:

Wiscott Aldrich syndrome

KLF1:

Kruppel-like factor 1

DN:

Double-negative

DP:

Double-positive (DP)

Treg:

Regulatory T

Teff:

Effector T

CTA:

Carboxy-terminal activation

SLE:

Systemic lupus erythematous

NKs:

Natural killer cells

PKCδ:

Protein kinase C-delta

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Acknowledgements

We would like to thank contribution of Chunlin Wang, Wuling Liu, and Analin Hu in preparation of this manuscript.

Funding

This work was supported by research grants from the Natural National Science Foundation of China (U1812403 and 21867009), the Science and Technology Department of Guizhou Province innovation and project grants (QKHPTRC[2019]5627), and the 100 Leading Talents of Guizhou Province to Y.B.-D.

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  1. State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Province Science City, High Tech Zone, Baiyun District, Guiyang, 550014, Guizhou Province, People’s Republic of China

    Yaacov Ben-David, Babu Gajendran & Klarke M. Sample

  2. The Key Laboratory of Chemistry for Natural Products of Guizhou Province, Chinese Academic of Sciences, Guiyang, 550014, Guizhou Province, People’s Republic of China

    Yaacov Ben-David, Babu Gajendran & Klarke M. Sample

  3. School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, 550025, Guizhou Province, People’s Republic of China

    Babu Gajendran

  4. Department of Medicine, University of Toronto, Toronto, ON, Canada

    Eldad Zacksenhaus

  5. Toronto General Research Institute, Max Bell Research Centre, University Health Network, 101 College Street, Toronto, ON, Canada

    Eldad Zacksenhaus

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Ben-David, Y., Gajendran, B., Sample, K.M. et al. Current insights into the role of Fli-1 in hematopoiesis and malignant transformation. Cell. Mol. Life Sci. 79, 163 (2022). https://doi.org/10.1007/s00018-022-04160-1

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