Journal Article

DKFZ-2025-00896

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The protein deacetylase HDAC10 controls DNA replication in malignant lymphoid cells.

Mieland, A. O. ; Petrosino, G. ; Dejung, M. ; Chen, J.-X. ; Fulzele, A. ; Mahmoudi, F. ; Tu, J.-W. ; Mustafa, A. M. ; Zeyn, Y. ; Hieber, C. ; Bros, M. ; Schnöder, T. M. ; Heidel, F. H. ; Najafi, S.DKFZ* ; Oehme, I.DKFZ* ; Hofmann, I.DKFZ* ; Schutkowski, M. ; Hilscher, S. ; Kosan, C. ; Butter, F. ; Bhatia, S. ; Sippl, W. ; Krämer, O. H.

2025
Springer Nature London

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Please use a persistent id in citations: doi:10.1038/s41375-025-02612-8

Abstract: 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.

Note: 2025 Jul;39(7):1756-1768

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Contributing Institute(s):

1. KKE Pädiatrische Onkologie (B310)
2. DKTK HD zentral (HD01)
3. Monoklonale Antikörper (W170)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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