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PLZF induces megakaryocytic development, activates Tpo receptor expression and interacts with GATA1 protein

Oncogene volume 21, pages 6669–6679 (2002) Cite this article

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Abstract

We investigated the expression of the PLZF gene in purified human hematopoietic progenitors induced to unilineage erythroid, granulocytic or megakaryocytic differentiation and maturation in serum-free culture. PLZF is expressed in quiescent progenitors: the expression level progressively rises through megakaryocytic development, whereas it gradually declines in erythroid and granulopoietic culture. To investigate the role of PLZF in megakaryopoiesis, we transduced the PLZF gene into the erythro-megakaryocytic TF1 cell line. PLZF overexpression upmodulates the megakaryocytic specific markers (CD42a, CD42b, CD61, PF4) and induces the thrombopoietin receptor (TpoR). The proximal promoter of the TpoR gene is activated in PLZF-expressing TF1 cells: in this promoter region, a PLZF DNA-binding site was identified by deletion constructs studies. Interestingly, PLZF and GATA1 proteins coimmunoprecipitate in PLZF-expressing TF1 cells: enforced expression of both PLZF and GATA1 in TF1 cells results in increased upregulation of megakaryocytic markers, as compared to exogenous PLZF or GATA1 alone, suggesting a functional role for the PLZF/GATA1 complex. Our data indicate that PLZF plays a significant stimulatory role in megakaryocytic development, seemingly mediated in part by induction of TpoR expression at transcriptional level. This stimulatory effect is potentiated by physical interaction of PLZF and GATA1, which are possibly assembled in a multiprotein transcriptional complex.

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Acknowledgements

We thank M Blasi and M Fontana for editorial assistance and A Zito and G Loreto for graphics. This work was partially supported by NIH grant CA 59936 to JD Licht.

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Authors and Affiliations

  1. Department of Hematology-Oncology, Istituto Superiore di Sanità, Rome, 00161, Italy

    Catherine Labbaye, Maria Teresa Quaranta, Alfredo Pagliuca, Stefania Militi, Ugo Testa & Cesare Peschle

  2. The Mount Sinai School of Medicine, New York, USA

    Jonathan D Licht

  3. T. Jefferson University, Philadelphia, USA

    Cesare Peschle

Authors
  1. Catherine Labbaye
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  2. Maria Teresa Quaranta
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  3. Alfredo Pagliuca
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  4. Stefania Militi
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  5. Jonathan D Licht
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  6. Ugo Testa
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  7. Cesare Peschle
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Correspondence to Catherine Labbaye.

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Labbaye, C., Quaranta, M., Pagliuca, A. et al. PLZF induces megakaryocytic development, activates Tpo receptor expression and interacts with GATA1 protein. Oncogene 21, 6669–6679 (2002). https://doi.org/10.1038/sj.onc.1205884

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