UMMS Affiliation

Program in Gene Function and Expression

Date

12-6-2006

Document Type

Article

Subjects

Acute Disease; Animals; Bone Marrow Cells; Cell Proliferation; Chromosomes, Human, Pair 16; Core Binding Factor beta Subunit; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Genotype; Heterozygote; Humans; Inversion, Chromosome; Kaplan-Meiers Estimate; Leukemia, Myeloid; Mice; Mice, Transgenic; Muscle, Smooth; Mutation; Myeloid Progenitor Cells; Myosin Heavy Chains; Oncogene Proteins, Fusion

Disciplines

Genetics and Genomics

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.

Rights and Permissions

Citation: Cancer Res. 2006 Dec 1;66(23):11214-8. Link to article on publisher's site

Related Resources

Link to article in PubMed

PubMed ID

17145866

 
 

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