Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation.

Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. Research Abstract Details 

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Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. Abstract Text:

Ting Xi Liu,Michael W Becker,Jaroslav Jelinek,Wen-Shu Wu,Min Deng,Natallia Mikhalkevich,Karl Hsu,Clara D Bloomfield,Richard M Stone,Daniel J DeAngelo,Ilene A Galinsky,Jean-Pierre Issa,Michael F Clarke,A Thomas Look,

Interstitial loss of all or part of the long arm of chromosome 5, or del(5q), is a frequent clonal chromosomal abnormality in human myelodysplastic syndrome (MDS, a preleukemic disorder) and acute myeloid leukemia (AML), and is thought to contribute to the pathogenesis of these diseases by deleting one or more tumor-suppressor genes. Although a major commonly deleted region (CDR) has been delineated on chromosome band 5q31.1 (refs. 3-7), attempts to identify tumor suppressors within this band have been unsuccessful. We focused our analysis of gene expression on RNA from primitive leukemia-initiating cells, which harbor 5q deletions, and analyzed 12 genes within the CDR that are expressed by normal hematopoietic stem cells. Here we show that the gene encoding alpha-catenin (CTNNA1) is expressed at a much lower level in leukemia-initiating stem cells from individuals with AML or MDS with a 5q deletion than in individuals with MDS or AML lacking a 5q deletion or in normal hematopoietic stem cells. Analysis of HL-60 cells, a myeloid leukemia line with deletion of the 5q31 region, showed that the CTNNA1 promoter of the retained allele is suppressed by both methylation and histone deacetylation. Restoration of CTNNA1 expression in HL-60 cells resulted in reduced proliferation and apoptotic cell death. Thus, loss of expression of the alpha-catenin tumor suppressor in hematopoietic stem cells may provide a growth advantage that contributes to human MDS or AML with del(5q).

Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. Publishing Authors By Initials

TX Liu,MW Becker,J Jelinek,WS Wu,M Deng,N Mikhalkevich,K Hsu,CD Bloomfield,RM Stone,DJ DeAngelo,IA Galinsky,JP Issa,MF Clarke,AT Look,

For similar proteins: cytoskeletal proteins: catenins: alpha catenin research abstracts see: proteins: cytoskeletal proteins: catenins: alpha catenin research

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Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Nature medicine

VOLUME: 13

Page Numbers: 78-83

Journal Abbreviation: Nat. Med.

ISSN: 1078-8956

DAY: 10

MONTH: 12

YEAR: 2006

Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9502015

Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. Keywords Mesh Terms:

KEYWORDS: alpha Catenin

MESH TERMS: metabolism

Chemical & Substance for Abstract: Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation. Information

Substance Name: trichostatin A

Registry Number: 58880-19-6

Grant and Affiliation Information for Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation.

AFFILIATION: Laboratory of Development and Diseases, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

Country: United States

AGENCY: United States NCI

GRANT: CA108631

ACRONYM: CA

MEDLINETA: Nat Med

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