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Fli-1 overexpression in erythroleukemic cells promotes erythroid de-differentiation while Spi-1/PU.1 exerts the opposite effect

  • Authors:
    • Laura M. Vecchiarelli-Federico
    • Tangjingjun Liu
    • Yao Yao
    • Yuanyuan Gao
    • Yanmei Li
    • You-Jun Li
    • Yaacov Ben-David
  • View Affiliations / Copyright

    Affiliations: Department of Medical Biophysics, University of Toronto, Toronto, Ontario M5G 1L7, Canada, The Key Laboratory of Chemistry for Natural Products of Guizhou Province and Chinese Academic of Sciences, Guiyang, Guizhou 550014, P.R. China, Department of Anatomy, College of Basic Medical Sciences, Jilin University, Changchun, Jilin 130021, P.R. China, Molecular and Cellular Biology, Sunnybrook Health Sciences Centre, Toronto, Ontario M4N 3M5, Canada
    Copyright: © Vecchiarelli-Federico et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 456-466
    |
    Published online on: June 2, 2017
       https://doi.org/10.3892/ijo.2017.4027
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Abstract

The ETS transcription factors play a critical role during hematopoiesis. In F-MuLV-induced erythroleukemia, Fli‑1 insertional activation producing high expression of this transcription factor required to promote proliferation. How deregulated Fli‑1 expression alters the balance between erythroid differentiation and proliferation is unknown. To address this issue, we exogenously overexpressed Fli‑1 in an erythroleukemic cell harboring activation of spi‑1/PU.1, another ETS gene involved in erythroleukemogenesis. While the proliferation in culture remains unaffected, Fli‑1 overexpression imparts morphological and immunohistochemical characteristics of immature erythroid progenitors. Fli‑1 overexpression in erythroleukemic cells increased the numbers of erythroid colonies on methylcellulose and reduced tumorigenicity as evidenced by increase latency of erythroleukemogenesis in mice inoculated with these cells. Although all transplanted mice developed enlargement of the spleen and liver due to leukemic infiltration, Fli‑1 overexpression altered the hematopoietic phenotype, significantly increasing the expression of regulatory hematopoietic genes cKIT, SCA-1, CD41 and CD71. In contrast, expression of Spi‑1/PU.1 in a Fli‑1 producing erythroleukemia cell line in which fli‑1 is activated, resulted in increased proliferation through activation of growth promoting proteins MAPK, AKT, cMYC and JAK2. Importantly, these progenitors express high levels of markers such as CD71 and TER119 associated with more mature erythroid cells. Thus, Fli‑1 overexpression induces a de-differentiation program by reverting CFU-E to BFU-E erythroid progenitor activity, while Spi‑1/PU.1 promoting maturation from BFU-E to CFU-E.
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Copy and paste a formatted citation
Spandidos Publications style
Vecchiarelli-Federico LM, Liu T, Yao Y, Gao Y, Li Y, Li Y and Ben-David Y: Fli-1 overexpression in erythroleukemic cells promotes erythroid de-differentiation while Spi-1/PU.1 exerts the opposite effect. Int J Oncol 51: 456-466, 2017.
APA
Vecchiarelli-Federico, L.M., Liu, T., Yao, Y., Gao, Y., Li, Y., Li, Y., & Ben-David, Y. (2017). Fli-1 overexpression in erythroleukemic cells promotes erythroid de-differentiation while Spi-1/PU.1 exerts the opposite effect. International Journal of Oncology, 51, 456-466. https://doi.org/10.3892/ijo.2017.4027
MLA
Vecchiarelli-Federico, L. M., Liu, T., Yao, Y., Gao, Y., Li, Y., Li, Y., Ben-David, Y."Fli-1 overexpression in erythroleukemic cells promotes erythroid de-differentiation while Spi-1/PU.1 exerts the opposite effect". International Journal of Oncology 51.2 (2017): 456-466.
Chicago
Vecchiarelli-Federico, L. M., Liu, T., Yao, Y., Gao, Y., Li, Y., Li, Y., Ben-David, Y."Fli-1 overexpression in erythroleukemic cells promotes erythroid de-differentiation while Spi-1/PU.1 exerts the opposite effect". International Journal of Oncology 51, no. 2 (2017): 456-466. https://doi.org/10.3892/ijo.2017.4027
Copy and paste a formatted citation
x
Spandidos Publications style
Vecchiarelli-Federico LM, Liu T, Yao Y, Gao Y, Li Y, Li Y and Ben-David Y: Fli-1 overexpression in erythroleukemic cells promotes erythroid de-differentiation while Spi-1/PU.1 exerts the opposite effect. Int J Oncol 51: 456-466, 2017.
APA
Vecchiarelli-Federico, L.M., Liu, T., Yao, Y., Gao, Y., Li, Y., Li, Y., & Ben-David, Y. (2017). Fli-1 overexpression in erythroleukemic cells promotes erythroid de-differentiation while Spi-1/PU.1 exerts the opposite effect. International Journal of Oncology, 51, 456-466. https://doi.org/10.3892/ijo.2017.4027
MLA
Vecchiarelli-Federico, L. M., Liu, T., Yao, Y., Gao, Y., Li, Y., Li, Y., Ben-David, Y."Fli-1 overexpression in erythroleukemic cells promotes erythroid de-differentiation while Spi-1/PU.1 exerts the opposite effect". International Journal of Oncology 51.2 (2017): 456-466.
Chicago
Vecchiarelli-Federico, L. M., Liu, T., Yao, Y., Gao, Y., Li, Y., Li, Y., Ben-David, Y."Fli-1 overexpression in erythroleukemic cells promotes erythroid de-differentiation while Spi-1/PU.1 exerts the opposite effect". International Journal of Oncology 51, no. 2 (2017): 456-466. https://doi.org/10.3892/ijo.2017.4027
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