%0 Journal Article
%A Mieland, Andreas O
%A Petrosino, Giuseppe
%A Dejung, Mario
%A Chen, Jia-Xuan
%A Fulzele, Amitkumar
%A Mahmoudi, Fereshteh
%A Tu, Jia-Wey
%A Mustafa, Al-Hassan M
%A Zeyn, Yanira
%A Hieber, Christoph
%A Bros, Matthias
%A Schnöder, Tina M
%A Heidel, Florian H
%A Najafi, Sara
%A Oehme, Ina
%A Hofmann, Ilse
%A Schutkowski, Mike
%A Hilscher, Sebastian
%A Kosan, Christian
%A Butter, Falk
%A Bhatia, Sanil
%A Sippl, Wolfgang
%A Krämer, Oliver H
%T The protein deacetylase HDAC10 controls DNA replication in malignant lymphoid cells.
%J Leukemia
%V 39
%N 7
%@ 0887-6924
%C London
%I Springer Nature
%M DKFZ-2025-00896
%P 1756-1768
%D 2025
%Z 2025 Jul;39(7):1756-1768
%X Histone deacetylases (HDACs) comprise a family of 18 epigenetic modifiers. The biologically relevant functions of HDAC10 in leukemia cells are enigmatic. We demonstrate that human cultured and primary acute B cell/T cell leukemia and lymphoma cells require the catalytic activity of HDAC10 for their survival. In such cells, HDAC10 controls a MYC-dependent transcriptional induction of the DNA polymerase subunit POLD1. Consequently, pharmacological inhibition of HDAC10 causes DNA breaks and an accumulation of poly-ADP-ribose chains. These processes culminate in caspase-dependent apoptosis. PZ48 does not damage resting and proliferating human normal blood cells. The in vivo activity of PZ48 against ALL cells is verified in a Danio rerio model. These data reveal a nuclear function for HDAC10. HDAC10 controls the MYC-POLD1 axis to maintain the processivity of DNA replication and genome integrity. This mechanistically defined 'HDAC10ness' may be exploited as treatment option for lymphoid malignancies.
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:40301616
%R 10.1038/s41375-025-02612-8
%U https://inrepo02.dkfz.de/record/300736