The H3K27me3 demethylase UTX is a gender-specific tumor suppressor in T-cell acute lymphoblastic leukemia

Author:

Van der Meulen Joni1,Sanghvi Viraj2,Mavrakis Konstantinos2,Durinck Kaat1,Fang Fang3,Matthijssens Filip1,Rondou Pieter1,Rosen Monica3,Pieters Tim14,Vandenberghe Peter5,Delabesse Eric6,Lammens Tim7,De Moerloose Barbara7,Menten Björn1,Van Roy Nadine1,Verhasselt Bruno8,Poppe Bruce1,Benoit Yves7,Taghon Tom8,Melnick Ari M.3,Speleman Frank1,Wendel Hans-Guido2,Van Vlierberghe Pieter1

Affiliation:

1. Center for Medical Genetics, Ghent University, Ghent, Belgium;

2. Cancer Biology and Genetics, Memorial Sloan-Kettering Cancer Center, New York, NY;

3. Department of Medicine, Weill Cornell Medical College, New York, NY;

4. Department for Biomedical Molecular Biology, Ghent University, Ghent, Belgium;

5. Centre for Human Genetics, University Hospital Leuven, Leuven, Belgium;

6. INSERM U563, Toulouse, France;

7. Department of Pediatric Hematology-Oncology and Stem Cell Transplantation, Ghent University Hospital, Ghent, Belgium; and

8. Department of Clinical Chemistry, Microbiology and Immunology, Ghent University, Ghent, Belgium

Abstract

Key Points The H3K27me3 demethylase UTX is recurrently mutated in male T-ALL and escapes X-inactivation in female T-ALL blasts and normal T cells. The loss of Utx contributes to T-ALL formation in vivo and UTX inactivation confers sensitivity to H3K27me3 inhibition.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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