Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemia View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2004-10

AUTHORS

C. Graux, J. Cools, C. Melotte, H. Quentmeier, A. Ferrando, R. Levine, J.R. Vermeesch, M. Stul, B. Dutta, N. Boeckx, A. Bosly, P. Heimann, A. Uyttebroeck, N. Mentens, R. Somers, R.A.F. MacLeod, H.G. Drexler, A.T. Look, D.G. Gilliland, L. Michaux, P. Vandenberghe, I. Wlodarska, Peter Marynen, Anne Hagemeijer

ABSTRACT

In T-cell acute lymphoblastic leukemia (T-ALL), transcription factors are known to be deregulated by chromosomal translocations, but mutations in protein tyrosine kinases have only rarely been identified. Here we describe the extrachromosomal (episomal) amplification of ABL1 in 5 of 90 (5.6%) individuals with T-ALL, an aberration that is not detectable by conventional cytogenetics. Molecular analyses delineated the amplicon as a 500-kb region from chromosome band 9q34, containing the oncogenes ABL1 and NUP214 (refs. 5,6). We identified a previously undescribed mechanism for activation of tyrosine kinases in cancer: the formation of episomes resulting in a fusion between NUP214 and ABL1. We detected the NUP214-ABL1 transcript in five individuals with the ABL1 amplification, in 5 of 85 (5.8%) additional individuals with T-ALL and in 3 of 22 T-ALL cell lines. The constitutively phosphorylated tyrosine kinase NUP214-ABL1 is sensitive to the tyrosine kinase inhibitor imatinib. The recurrent cryptic NUP214-ABL1 rearrangement is associated with increased HOX expression and deletion of CDKN2A, consistent with a multistep pathogenesis of T-ALL. NUP214-ABL1 expression defines a new subgroup of individuals with T-ALL who could benefit from treatment with imatinib. More... »

PAGES

1084-1089

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/ng1425

DOI

http://dx.doi.org/10.1038/ng1425

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1000325804

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/15361874


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