%0 Journal Article
%A Smith, Charlotte
%A Touzart, Aurore
%A Simonin, Mathieu
%A Tran-Quang, Christine
%A Hypolite, Guillaume
%A Latiri, Mehdi
%A Andrieu, Guillaume P
%A Balducci, Estelle
%A Dourthe, Marie-Émilie
%A Goyal, Ashish
%A Huguet, Françoise
%A Petit, Arnaud
%A Ifrah, Norbert
%A Baruchel, André
%A Dombret, Hervé
%A Macintyre, Elizabeth
%A Plass, Christoph
%A Ghysdael, Jacques
%A Boissel, Nicolas
%A Asnafi, Vahid
%T Harnessing the MYB-dependent TAL1 5'super-enhancer for targeted therapy in T-ALL.
%J Molecular cancer
%V 22
%N 1
%@ 1476-4598
%C London
%I Biomed Central
%M DKFZ-2023-00111
%P 12
%D 2023
%X 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.
%K Cancer (Other)
%K Oncogene (Other)
%K Super-enhancer (Other)
%K Targeted therapy (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:36650499
%R 10.1186/s12943-022-01701-x
%U https://inrepo02.dkfz.de/record/186783