Plag1 and Plagl2 are oncogenes that induce acute myeloid leukemia in cooperation with Cbfb-MYH11

S.F. Landrette, Y.H. Kuo, K. Hensen, S.B. van Waalwijk van Doorn-Khosrovani, P.N. Perrat, W.J. van de Ven, R. Delwel, L.H. Castilla

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Abstract

Plag1 and Plagl2 are oncogenes that induce acute myeloid leukemia in cooperation with Cbfb-MYH11.

Landrette SF, Kuo YH, Hensen K, Khosrovani B, Perrat PN, Van de Ven WJ, Delwel R, Castilla LH.

Program in Gene Function and Expression, University od Massachusetts Medical School, Worcester, Massachusetts, USA.

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 inducing leukemia upon the acquisition of additional mutations. A recent genetic screen identified Plag1 and Plagl2 as CBFbeta-SMMHC candidate cooperating proteins. In this study, we demonstrate that Plag1 and Plagl2 independently cooperate with CBFbeta-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 phase 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.
Original languageEnglish
Pages (from-to)2900-2907
JournalBlood
Volume105
Issue number7
DOIs
Publication statusPublished - 1 Jan 2005

Cite this

Landrette, S. F., Kuo, Y. H., Hensen, K., van Waalwijk van Doorn-Khosrovani, S. B., Perrat, P. N., van de Ven, W. J., Delwel, R., & Castilla, L. H. (2005). Plag1 and Plagl2 are oncogenes that induce acute myeloid leukemia in cooperation with Cbfb-MYH11. Blood, 105(7), 2900-2907. https://doi.org/10.1182/blood-2004-09-3630