The recurrent SET-NUP214 fusion as a new HOXA activation mechanism in pediatric T-cell acute lymphoblastic leukemia

Pieter Van Vlierberghe, Martine Van Grotel, Joëlle Tchinda, Charles Lee, H. Berna Beverloo, Peter J. Van Der Spek, Andrew Stubbs, Jan Cools, Kyosuke Nagata, Maarten Fornerod, Jessica Buijs-Gladdines, Martin Horstmann, Elisabeth R. Van Wering, Jean Soulier, Rob Pieters, Jules P.P. Meijerink

Onderzoeksoutput: Bijdrage aan tijdschriftArtikelpeer review

185 Citaten (Scopus)


T-cell acute lymphoblastic leukemia (TALL) is mostly characterized by specific chromosomal abnormalities, some occurring in a mutually exclusive manner that possibly delineate specific T-ALL subgroups. One subgroup, including MLLrearranged, CALM-AFWor inv (7)(p15q34) patients, is characterized by elevated expression of HOXA genes. Using a gene expression-based clustering analysis of 67 T-ALL cases with recurrent molecular genetic abnormalities and 25 samples lacking apparent aberrations, we identified 5 new patients with elevated HOXA levels. Using microarray-based comparative genomic hybridization (array-CGH), a cryptic and recurrent deletion, del (9)(q34.11q34.13), was exclusively identified in 3 of these 5 patients. This deletion results in a conserved SET-NUP214 fusion product, which was also identified in the T-ALL cell line LOUCY. SET-NUP214 binds in the promoter regions of specific HOXA genes, where it interacts with CRM1 and DOT1L, which may transcriptionally activate specific members of the HOXA cluster. Targeted inhibition of SET-NUP214 by siRNA abolished expression of HOXA genes, inhibited proliferation, and induced differentiation in LOUCY but not in other T-ALL lines. We conclude that SETNUP214 may contribute to the pathogenesis of T-ALL by enforcing T-cell differentia.

Originele taal-2Engels
Pagina's (van-tot)4668-4680
Aantal pagina's13
Nummer van het tijdschrift9
StatusGepubliceerd - 1 mei 2008
Extern gepubliceerdJa


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