Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation
- PMID: 17159988
- DOI: 10.1038/nm1512
Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation
Abstract
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).
Similar articles
-
Progressive chromatin repression and promoter methylation of CTNNA1 associated with advanced myeloid malignancies.Cancer Res. 2009 Nov 1;69(21):8482-90. doi: 10.1158/0008-5472.CAN-09-1153. Epub 2009 Oct 13. Cancer Res. 2009. PMID: 19826047 Free PMC article.
-
5q- myelodysplastic syndromes: chromosome 5q genes direct a tumor-suppression network sensing actin dynamics.Oncogene. 2009 Oct 1;28(39):3429-41. doi: 10.1038/onc.2009.207. Epub 2009 Jul 13. Oncogene. 2009. PMID: 19597464 Review.
-
A novel nuclear protein, 5qNCA (LOC51780) is a candidate for the myeloid leukemia tumor suppressor gene on chromosome 5 band q31.Oncogene. 2001 Oct 18;20(47):6946-54. doi: 10.1038/sj.onc.1204850. Oncogene. 2001. PMID: 11687974
-
Susceptibility gene for familial acute myeloid leukemia associated with loss of 5q and/or 7q is not localized on the commonly deleted portion of 5q.Genes Chromosomes Cancer. 2000 Jun;28(2):164-72. Genes Chromosomes Cancer. 2000. PMID: 10825001
-
Deletions of chromosome 5 in malignant myeloid disorders.Cancer Surv. 1992;15:143-59. Cancer Surv. 1992. PMID: 1451109 Review.
Cited by
-
DELE1 haploinsufficiency causes resistance to mitochondrial stress-induced apoptosis in monosomy 5/del(5q) AML.Leukemia. 2024 Mar;38(3):530-537. doi: 10.1038/s41375-023-02107-4. Epub 2023 Dec 15. Leukemia. 2024. PMID: 38102204 Free PMC article.
-
α-catenin interaction with YAP/FoxM1/TEAD-induced CEP55 supports liver cancer cell migration.Cell Commun Signal. 2023 Jun 28;21(1):162. doi: 10.1186/s12964-023-01169-2. Cell Commun Signal. 2023. PMID: 37381005 Free PMC article.
-
The Role of CTNNA1 in Malignancies: An Updated Review.J Cancer. 2023 Jan 1;14(2):219-230. doi: 10.7150/jca.79236. eCollection 2023. J Cancer. 2023. PMID: 36741258 Free PMC article. Review.
-
Pathophysiologic and clinical implications of molecular profiles resultant from deletion 5q.EBioMedicine. 2022 Jun;80:104059. doi: 10.1016/j.ebiom.2022.104059. Epub 2022 May 23. EBioMedicine. 2022. PMID: 35617825 Free PMC article.
-
Genome-wide DNA methylation analysis pre- and post-lenalidomide treatment in patients with myelodysplastic syndrome with isolated deletion (5q).Ann Hematol. 2021 Jun;100(6):1463-1471. doi: 10.1007/s00277-021-04492-1. Epub 2021 Apr 27. Ann Hematol. 2021. PMID: 33903952 Free PMC article. Clinical Trial.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous