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The complex genomic profile of ETV6-RUNX1 positive acute lymphoblastic leukemia highlights a recurrent deletion of TBL1XR1

Lookup NU author(s): Marian Case, Dr Tina Davies, Professor Anthony MoormanORCiD, Dr Andrew Hall, Professor Julie Irving, Professor Christine Harrison FRCPath FMedSci


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The ETV6-RUNX1 fusion is the molecular consequence of the t(12;21)(p13;q22) seen in approximately 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.

Publication metadata

Author(s): Parker H, An Q, Barber K, Case MC, Davies TL, Konn Z, Stewart A, Wright S, Griffiths M, Ross FM, Moorman AV, Hall AG, Irving JAE, Harrison CJ, Strefford JC

Publication type: Article

Publication status: Published

Journal: Genes, Chromosomes and Cancer

Year: 2008

Volume: 47

Issue: 12

Pages: 1118-1125

ISSN (print): 1045-2257

ISSN (electronic): 1098-2264

Publisher: John Wiley & Sons, Inc.


DOI: 10.1002/gcc.20613

Notes: Journal Article Research Support, Non-U.S. Gov't United States


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