Title: The H3K27me3 demethylase UTX is a gender-specific tumor suppressor in T-cell acute lymphoblastic leukemia
Authors: Van der Meulen, Joni ×
Sanghvi, Viraj
Mavrakis, Konstantinos
Durinck, Kaat
Fang, Fang
Matthijssens, Filip
Rondou, Pieter
Vandenberghe, Peter
Delabesse, Eric
Lammens, Tim
De Moerloose, Barbara
Menten, Björn
Van Roy, Nadine
Verhasselt, Bruno
Poppe, Bruce
Benoit, Yves
Taghon, Tom
Melnick, Ari
Speleman, Frank
Wendel, Hans-Guido
Van Vlierberghe, Pieter #
Issue Date: Jan-2015
Series Title: Blood vol:125 issue:1 pages:13-21
Article number: blood-2014-05-577270
Abstract: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive form of leukemia that is mainly diagnosed in children and shows a skewed gender distribution towards males. Here, we report somatic loss-of-function mutations in the X-linked histone H3K27me3 demethylase UTX in human T-ALL. Interestingly, UTX mutations were exclusively present in male T-ALL patients and allelic expression analysis revealed that UTX escapes X-inactivation in female T-ALL lymphoblasts and normal T-cells. Notably, we demonstrate in vitro and in vivo that the H3K27me3 demethylase Utx functions as a bona fide tumor suppressor in T-ALL. Moreover, T-ALL driven by UTX inactivation exhibits collateral sensitivity to pharmacological H3K27me3 inhibition. All together, our results show how a gender-specific and therapeutically relevant defect in balancing H3K27 methylation contributes to T-cell leukemogenesis.
ISSN: 0006-4971
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
× corresponding author
# (joint) last author

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