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The complex genomic profile of ETV6-RUNX1 positive acute lymphoblastic leukemia highlights a recurrent deletion of TBLIXR1

The complex genomic profile of ETV6-RUNX1 positive acute lymphoblastic leukemia highlights a recurrent deletion of TBLIXR1
The complex genomic profile of ETV6-RUNX1 positive acute lymphoblastic leukemia highlights a recurrent deletion of TBLIXR1
The ETV6-RUNX1 fusion is the molecular consequence of the t(12;21)(p13;q22) seen in similar to 25% of children with acute lymphoblastic leukemia (ALL). Studies have shown that the fusion alone is insufficient for the initiation of leukemia; additional genetic changes are required. Genomic profiling identified copy number alterations at high frequencies in these patients. Focal deletions of TBL1XR1 were observed in 15% of cases; 3 patients exhibited deletions distal to the gene. Fluorescence in situ hybridization confirmed these deletions and quantitative RT-PCR showed that the TBL1XR1 gene was significantly under-expressed. TBL1XR1 is a key component of the SMRT and N-CoR compressor complexes, which control hormone-receptor mediated gene expression. Differential expression of the retinoic acid target genes, RARB, CRABP1, and CRABP2, indicated that deletion of TBL1XR1 compromised the function of SMRT/N-CoR in the appropriate control of gene expression. This study identifies deletions of TBL1XR1 as a recurrent abnormality in ETV6-RUNX1 positive ALL. We provide evidence that implicates this deletion in the inappropriate control of gene expression in these patients. The target of the interaction between TBL1XR1 and the signaling pathways described here may be exploited in cancer therapy. (C) 2008 Wiley-Liss, Inc ISSN/ISBN: 1045-2257 WEB/URL: PM:18767146;
therapy, acute promyelocytic leukemia, leukemia, fluorescence, n-cor, acid-binding protein, in-vitro, deletions, expression, prognostic-significance, time, children, gene, acid, cancer, tel-aml1 gene fusion, chromosome translocations, patients, england, in situ hybridization, gene expression, retinoic acid, genes, tel gene, abnormalities
1045-2257
1118-1125
Parker, Helen
33e0cd81-d45f-49bc-9539-09345d79d895
An, Qian
6766de29-63b7-45eb-b21a-04cac9921373
Barber, Kerry
a0901e6e-4b25-4d58-bffe-cbc4608d0847
Case, Marian
81f27d29-1d48-442f-a054-4d40f1abac47
Davies, Teresa
7feaa1c8-4ab7-4ac9-b350-136c8bc4af34
Konn, Zoë
525b4648-7c88-488a-aefa-0018ac485eb4
Stewart, Adam
804d4d6f-7e4c-482a-8216-424761ab56c0
Wright, Sarah
775184e7-df20-4253-86c9-90d25e2b104c
Griffiths, Mike
f147af96-79ab-43ef-984c-550407b82c39
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
Moorman, Anthony V.
e4ced178-ee03-47ef-bc5e-25d8453951d5
Hall, Andy G.
ba5c3115-a875-44ed-87f7-61d0cbdb6e99
Irving, Julie A.
94a0fe3e-5344-4523-aa2a-98969f5c6ebd
Harrison, Christine J.
52da7673-509c-4b88-b92e-0c021c9c7d3e
Strefford, Jon C.
3782b392-f080-42bf-bdca-8aa5d6ca532f
Parker, Helen
33e0cd81-d45f-49bc-9539-09345d79d895
An, Qian
6766de29-63b7-45eb-b21a-04cac9921373
Barber, Kerry
a0901e6e-4b25-4d58-bffe-cbc4608d0847
Case, Marian
81f27d29-1d48-442f-a054-4d40f1abac47
Davies, Teresa
7feaa1c8-4ab7-4ac9-b350-136c8bc4af34
Konn, Zoë
525b4648-7c88-488a-aefa-0018ac485eb4
Stewart, Adam
804d4d6f-7e4c-482a-8216-424761ab56c0
Wright, Sarah
775184e7-df20-4253-86c9-90d25e2b104c
Griffiths, Mike
f147af96-79ab-43ef-984c-550407b82c39
Ross, Fiona M.
ec0958f8-b992-4e4a-b7e3-c474600390ba
Moorman, Anthony V.
e4ced178-ee03-47ef-bc5e-25d8453951d5
Hall, Andy G.
ba5c3115-a875-44ed-87f7-61d0cbdb6e99
Irving, Julie A.
94a0fe3e-5344-4523-aa2a-98969f5c6ebd
Harrison, Christine J.
52da7673-509c-4b88-b92e-0c021c9c7d3e
Strefford, Jon C.
3782b392-f080-42bf-bdca-8aa5d6ca532f

Parker, Helen, An, Qian, Barber, Kerry, Case, Marian, Davies, Teresa, Konn, Zoë, Stewart, Adam, Wright, Sarah, Griffiths, Mike, Ross, Fiona M., Moorman, Anthony V., Hall, Andy G., Irving, Julie A., Harrison, Christine J. and Strefford, Jon C. (2008) The complex genomic profile of ETV6-RUNX1 positive acute lymphoblastic leukemia highlights a recurrent deletion of TBLIXR1. Genes, Chromosomes and Cancer, 47 (12), 1118-1125. (doi:10.1002/gcc.20613).

Record type: Article

Abstract

The ETV6-RUNX1 fusion is the molecular consequence of the t(12;21)(p13;q22) seen in similar to 25% of children with acute lymphoblastic leukemia (ALL). Studies have shown that the fusion alone is insufficient for the initiation of leukemia; additional genetic changes are required. Genomic profiling identified copy number alterations at high frequencies in these patients. Focal deletions of TBL1XR1 were observed in 15% of cases; 3 patients exhibited deletions distal to the gene. Fluorescence in situ hybridization confirmed these deletions and quantitative RT-PCR showed that the TBL1XR1 gene was significantly under-expressed. TBL1XR1 is a key component of the SMRT and N-CoR compressor complexes, which control hormone-receptor mediated gene expression. Differential expression of the retinoic acid target genes, RARB, CRABP1, and CRABP2, indicated that deletion of TBL1XR1 compromised the function of SMRT/N-CoR in the appropriate control of gene expression. This study identifies deletions of TBL1XR1 as a recurrent abnormality in ETV6-RUNX1 positive ALL. We provide evidence that implicates this deletion in the inappropriate control of gene expression in these patients. The target of the interaction between TBL1XR1 and the signaling pathways described here may be exploited in cancer therapy. (C) 2008 Wiley-Liss, Inc ISSN/ISBN: 1045-2257 WEB/URL: PM:18767146;

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More information

Published date: 2008
Keywords: therapy, acute promyelocytic leukemia, leukemia, fluorescence, n-cor, acid-binding protein, in-vitro, deletions, expression, prognostic-significance, time, children, gene, acid, cancer, tel-aml1 gene fusion, chromosome translocations, patients, england, in situ hybridization, gene expression, retinoic acid, genes, tel gene, abnormalities
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 70782
URI: http://eprints.soton.ac.uk/id/eprint/70782
ISSN: 1045-2257
PURE UUID: 3d1d3214-47b5-4db1-ad38-fe3856ca72b8
ORCID for Helen Parker: ORCID iD orcid.org/0000-0001-8308-9781
ORCID for Jon C. Strefford: ORCID iD orcid.org/0000-0002-0972-2881

Catalogue record

Date deposited: 06 Jan 2010
Last modified: 14 Mar 2024 02:49

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Contributors

Author: Helen Parker ORCID iD
Author: Qian An
Author: Kerry Barber
Author: Marian Case
Author: Teresa Davies
Author: Zoë Konn
Author: Adam Stewart
Author: Sarah Wright
Author: Mike Griffiths
Author: Fiona M. Ross
Author: Anthony V. Moorman
Author: Andy G. Hall
Author: Julie A. Irving
Author: Christine J. Harrison

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