Journal Article

DKFZ-2023-00111

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Harnessing the MYB-dependent TAL1 5'super-enhancer for targeted therapy in T-ALL.

Smith, C. ; Touzart, A. ; Simonin, M. ; Tran-Quang, C. ; Hypolite, G. ; Latiri, M. ; Andrieu, G. P. ; Balducci, E. ; Dourthe, M.-É. ; Goyal, A.DKFZ* ; Huguet, F. ; Petit, A. ; Ifrah, N. ; Baruchel, A. ; Dombret, H. ; Macintyre, E. ; Plass, C.DKFZ* ; Ghysdael, J. ; Boissel, N. ; Asnafi, V.

2023
Biomed Central London

This record in other databases:  

Please use a persistent id in citations: doi:10.1186/s12943-022-01701-x

Abstract: The acquisition of genetic abnormalities engendering oncogene dysregulation underpins cancer development. Certain proto-oncogenes possess several dysregulation mechanisms, yet how each mechanism impacts clinical outcome is unclear. Using T-cell acute lymphoblastic leukemia (T-ALL) as an example, we show that patients harboring 5'super-enhancer (5'SE) mutations of the TAL1 oncogene identifies a specific patient subgroup with poor prognosis irrespective of the level of oncogene dysregulation. Remarkably, the MYB dependent oncogenic 5'SE can be targeted using Mebendazole to induce MYB protein degradation and T-ALL cell death. Of note Mebendazole treatment demonstrated efficacy in vivo in T-ALL preclinical models. Our work provides proof of concept that within a specific oncogene driven cancer, the mechanism of oncogene dysregulation rather than the oncogene itself can identify clinically distinct patient subgroups and pave the way for future super-enhancer targeting therapy.

Keyword(s): Cancer ; Oncogene ; Super-enhancer ; Targeted therapy

---

Contributing Institute(s):

1. Epigenomik (B370)
2. DKTK HD zentral (HD01)

Research Program(s):

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

Appears in the scientific report 2023

---

Database coverage:
; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 30 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---