The transcription factor PlagL2 activates Mpl transcription and signaling in hematopoietic progenitor and leukemia cells
UMass Chan AffiliationsDepartment of Microbiology and Physiologic Systems
Program in Gene Function and Expression
KeywordsLeukemia, Myeloid, Acute
Oncogene Proteins, Fusion
Core Binding Factor beta Subunit
Gene Expression Regulation
Genetics and Genomics
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AbstractCytokine 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 Cbfbeta-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 Cbfbeta-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 CBFbeta-SMMHC in mice.
SourceLeukemia. 2011 Apr;25(4):655-62. Epub 2011 Jan 25. Link to article on publisher's site
Permanent Link to this Itemhttp://hdl.handle.net/20.500.14038/43939
Co-author Dmitri Madera is a student in the Graduate School of Biomedical Sciences (GSBS) at UMass Medical School.
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