Title: The recurrent SET-NUP214 fusion as a new HOXA activation mechanism in pediatric T-cell acute lymphoblastic leukemia
Authors: Van Vlierberghe, Pieter
van Grotel, Martine
Tchinda, Joelle
Lee, Charles
Beverloo, H. Berna
van der Spek, Peter J
Stubbs, Andrew
Cools, Jan
Nagata, Kyosuke
Fornerod, Maarten
Buijs-Gladdines, Jessica
Horstmann, Martin
van Wering, Elisabeth R
Soulier, Jean
Pieters, Rob
Meijerink, Jules P. P # ×
Issue Date: May-2008
Publisher: Amer soc hematology
Series Title: Blood vol:111 issue:9 pages:4668-4680
Abstract: 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 MLL-rearranged, CALM-AF10 or 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 differentiation arrest.
ISSN: 0006-4971
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Genetics Section (-)
Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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