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Oncogenes, Fusion Genes and Tumor Suppressor Genes

The transcription factor PlagL2 activates Mpl transcription and signaling in hematopoietic progenitor and leukemia cells

Leukemia volume 25, pages 655–662 (2011)Cite this article

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Abstract

Cytokine signaling pathways are frequent targets of oncogenic mutations in acute myeloid leukemia (AML), promoting proliferation and survival. We have previously shown that the transcription factor PLAGL2 promotes proliferation and cooperates with the leukemia fusion protein Cbfβ-SMMHC in AML development. Here, we show that PLAGL2 upregulates expression of the thrombopoietin receptor Mpl, using two consensus sites in its proximal promoter. We also show that Mpl overexpression efficiently cooperates with Cbfβ-SMMHC in development of leukemia in mice. Finally, we demonstrate that PlagL2-expressing leukemic cells show hyper-activation of Jak2 and downstream STAT5, Akt and Erk1/2 pathways in response to Thpo ligand. These results show that PlagL2 expression activates expression of Mpl in hematopoietic progenitors, and that upregulation of wild-type Mpl provides an oncogenic signal in cooperation with CBFβ-SMMHC in mice.

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Acknowledgements

We thank Julie Zhu and Stephen Baker for the statistical analyses of the expression data. This work was supported by National Institutes of Health Grant CA09683 to LHC, and Core resources were supported by the Diabetes Endocrinology Research Center Grant DK32520. LHC is recipient of a Scholar Award from the Leukemia and Lymphoma Society.

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Author notes

  1. S F Landrette

    Present address: 4Current address: Yale School of Medicine, 295 Congress Avenue, New Haven, CT 06519, USA.,

  2. S F Landrette and D Madera: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Molecular Medicine, Program in Gene Function and Expression, University of Massachusetts Medical School, Worcester, MA, USA

    S F Landrette, D Madera & L H Castilla

  2. Department of Microbiology and Physiologic Systems, University of Massachusetts Medical School, Worcester, MA, USA

    F He

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  1. S F Landrette
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  2. D Madera
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Correspondence to L H Castilla.

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Landrette, S., Madera, D., He, F. et al. The transcription factor PlagL2 activates Mpl transcription and signaling in hematopoietic progenitor and leukemia cells. Leukemia 25, 655–662 (2011). https://doi.org/10.1038/leu.2010.301

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