Cbfbeta reduces Cbfbeta-SMMHC-associated acute myeloid leukemia in mice.

Abstract	The gene encoding for core-binding factor beta (CBFbeta) is altered in acute myeloid leukemia samples with an inversion in chromosome 16, expressing the fusion protein CBFbeta-SMMHC. Previous studies have shown that this oncoprotein interferes with hematopoietic differentiation and proliferation and participates in leukemia development. In this study, we provide evidence that Cbfbeta modulates the oncogenic function of this fusion protein. We show that Cbfbeta plays an important role in proliferation of hematopoietic progenitors expressing Cbfbeta-SMMHC in vitro. In addition, Cbfbeta-SMMHC-mediated leukemia development is accelerated in the absence of Cbfbeta. These results indicate that the balance between Cbfbeta and Cbfbeta-SMMHC directly affects leukemia development, and suggest that CBF-specific therapeutic molecules should target CBFbeta-SMMHC function while maintaining CBFbeta activity.
Authors	Susan A Heilman, Ya-Huei Kuo, Chantal S Goudswaard, Peter J Valk, Lucio H Castilla
Journal	Cancer research (Cancer Res) Vol. 66 Issue 23 Pg. 11214-8 (Dec 01 2006) ISSN: 0008-5472 [Print] United States
PMID	17145866 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References	CBFB protein, human CBFbeta-MYH11 fusion protein Cbfb protein, mouse Core Binding Factor beta Subunit Oncogene Proteins, Fusion Myosin Heavy Chains
Topics	Acute Disease Animals Bone Marrow Cells (metabolism) Cell Proliferation Chromosome Inversion Chromosomes, Human, Pair 16 (genetics) Core Binding Factor beta Subunit (genetics, metabolism) Gene Expression Regulation, Neoplastic Genetic Predisposition to Disease (genetics) Genotype Heterozygote Humans Kaplan-Meier Estimate Leukemia, Myeloid (genetics, metabolism, pathology) Mice Mice, Transgenic Muscle, Smooth (chemistry) Mutation (genetics) Myeloid Progenitor Cells (metabolism) Myosin Heavy Chains (genetics, metabolism) Oncogene Proteins, Fusion (genetics, metabolism)

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