Title: 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, Willem
Delwel, Ruud
Castilla, Lucio H #
Issue Date: Mar-2005
Series Title: Blood vol:105 issue:7 pages:2900-7
Abstract: 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.
ISSN: 0006-4971
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Associated Laboratories - miscellaneous (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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