Delineation of a minimal interval and identification of 9 candidates for a tumor suppressor gene in malignant myeloid disorders on 5q31
- PMID: 10733509
Delineation of a minimal interval and identification of 9 candidates for a tumor suppressor gene in malignant myeloid disorders on 5q31
Abstract
Interstitial deletion or loss of chromosome 5 is frequent in malignant myeloid disorders, including myelodysplasia (MDS) and acute myeloid leukemia (AML), suggesting the presence of a tumor suppressor gene. Loss of heterozygosity (LOH) analysis was used to define a minimal deletion interval for this gene. Polymorphic markers on 5q31 were identified using a high-resolution physical and radiation hybrid breakpoint map and applied to a patient with AML with a subcytogenetic deletion of 5q. By comparing the DNA from leukemic cells to buccal mucosa cells, LOH was detected with markers D5S476 and D5S1372 with retention of flanking markers D5S500 to D5S594. The D5S500-D5S594 interval, which covers approximately 700 kb, thus represents a minimal localization for the tumor suppressor gene. Further refinement of the physical map enabled the specification of 9 transcription units within the encompassing radiation hybrid bins and 7 in flanking bins. The 9 candidates include genes CDC25, HSPA9, EGR1, CTNNA1, and 5 unknown ESTs. Reverse-transcription polymerase chain reaction confirms that all of them are expressed in normal human bone marrow CD34(+) cells and in AML cell lines and thus represent likely candidates for the MDS-AML tumor suppressor gene at 5q31.
Similar articles
-
Polymerase chain reaction-based diagnosis of del (5q) in acute myeloid leukemia and myelodysplastic syndrome identifies a minimal deletion interval.Blood. 1996 Oct 1;88(7):2665-70. Blood. 1996. PMID: 8839861
-
Chromosome 5q deletion and epigenetic suppression of the gene encoding alpha-catenin (CTNNA1) in myeloid cell transformation.Nat Med. 2007 Jan;13(1):78-83. doi: 10.1038/nm1512. Epub 2006 Dec 10. Nat Med. 2007. PMID: 17159988
-
Deletions of PURA, at 5q31, and PURB, at 7p13, in myelodysplastic syndrome and progression to acute myelogenous leukemia.Leukemia. 2001 Jun;15(6):954-62. doi: 10.1038/sj.leu.2402108. Leukemia. 2001. PMID: 11417483
-
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.
-
Molecular analysis of the 5q- chromosome.Leuk Lymphoma. 1995 May;17(5-6):361-6. doi: 10.3109/10428199509056846. Leuk Lymphoma. 1995. PMID: 7549826 Review.
Cited by
-
Identification of PITX1 as a TERT suppressor gene located on human chromosome 5.Mol Cell Biol. 2011 Apr;31(8):1624-36. doi: 10.1128/MCB.00470-10. Epub 2011 Feb 7. Mol Cell Biol. 2011. PMID: 21300782 Free PMC article.
-
Identification of RPS14 as a 5q- syndrome gene by RNA interference screen.Nature. 2008 Jan 17;451(7176):335-9. doi: 10.1038/nature06494. Nature. 2008. PMID: 18202658 Free PMC article.
-
Advances in treating acute myeloid leukemia.F1000Prime Rep. 2014 Oct 1;6:96. doi: 10.12703/P6-96. eCollection 2014. F1000Prime Rep. 2014. PMID: 25374674 Free PMC article. Review.
-
Targeting low-risk myelodysplastic syndrome with novel therapeutic strategies.Trends Mol Med. 2021 Oct;27(10):990-999. doi: 10.1016/j.molmed.2021.06.013. Epub 2021 Jul 11. Trends Mol Med. 2021. PMID: 34257007 Free PMC article. Review.
-
EGR-1/ASPP1 inter-regulatory loop promotes apoptosis by inhibiting cyto-protective autophagy.Cell Death Dis. 2017 Jun 8;8(6):e2869. doi: 10.1038/cddis.2017.268. Cell Death Dis. 2017. PMID: 28594407 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical
Research Materials
Miscellaneous
