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

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 Cbf?-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 Cbf?-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 CBF?-SMMHC in mice.

SUBMITTER: Landrette SF

PROVIDER: S-EPMC3076538 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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

Landrette S F SF Madera D D He F F Castilla L H LH

Leukemia 20110125 4

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 coopera ...[more]

PMID: 21263445

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