Plag1 and Plagl2 are oncogenes that induce acute myeloid leukemia in cooperation with Cbfb-MYH11
Authors
Landrette, Sean F.Kuo, Ya-Huei
Hensen, Karen
Barjesteh van Waalwijk van Doorn-Khosrovani, Sahar
Perrat, Paola N.
Van de Ven, Wim J. M.
Delwel, Ruud
Castilla, Lucio H.
Student Authors
Paola PerratAcademic Program
NeuroscienceDocument Type
Journal ArticlePublication Date
2004-12-09Keywords
Acute DiseaseAdolescent
Adult
Animals
DNA-Binding Proteins
Female
G1 Phase
Gene Expression Regulation, Leukemic
Hematopoietic Stem Cells
Humans
Leukemia, Myeloid
Male
Mice
Mice, Mutant Strains
Middle Aged
Mutagenesis, Insertional
Oncogene Proteins, Fusion
RNA-Binding Proteins
Retroviridae
S Phase
Transcription Factors
Genetics and Genomics
Neuroscience and Neurobiology
Metadata
Show full item recordAbstract
Recurrent chromosomal rearrangements are associated with the development of acute myeloid leukemia (AML). The frequent inversion of chromosome 16 creates the CBFB-MYH11 fusion gene that encodes the fusion protein CBFbeta-SMMHC. This fusion protein inhibits the core-binding factor (CBF), resulting in a block of hematopoietic differentiation, and induces leukemia upon the acquisition of additional mutations. A recent genetic screen identified Plag1 and Plagl2 as CBF beta-SMMHC candidate cooperating proteins. In this study, we demonstrate that Plag1 and Plagl2 independently cooperate with CBF beta-SMMHC in vivo to efficiently trigger leukemia with short latency in the mouse. In addition, Plag1 and Plagl2 increased proliferation by inducing G1 to S transition that resulted in the expansion of hematopoietic progenitors and increased cell renewal in vitro. Finally, PLAG1 and PLAGL2 expression was increased in 20% of human AML samples. Interestingly, PLAGL2 was preferentially increased in samples with chromosome 16 inversion, suggesting that PLAG1 and PLAGL2 may also contribute to human AML. Overall, this study shows that Plag1 and Plagl2 are novel leukemia oncogenes that act by expanding hematopoietic progenitors expressing CbF beta-SMMHC.Source
Blood. 2005 Apr 1;105(7):2900-7. Epub 2004 Dec 7. Link to article on publisher's siteDOI
10.1182/blood-2004-09-3630Permanent Link to this Item
http://hdl.handle.net/20.500.14038/39960PubMed ID
15585652Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1182/blood-2004-09-3630