| Literature DB >> 31751766 |
Aline Massé1, Louise Roulin1, Justine Pasanisi1, Justine Penneroux1, Stéphanie Gachet1, Marc Delord2, Ashfaq Ali1, Antonio Alberdi3, Jeannig Berrou4, Marie Passet5, Lucie Hernandez5, Samuel Quentin5, Claude Gardin6, Emmanuel Raffoux7, Lionel Adès8, Thorsten Braun6, Jean Soulier5, Emmanuelle Clappier5, Hervé Dombret9, Alexandre Puissant1, Raphael Itzykson10.
Abstract
Bromodomain and Extra-Terminal inhibitors (BETi) such as OTX015 are active in Acute Myeloid Leukaemias (AML). Their activity on Leukemic Stem Cells (LSCs) is less documented. We interrogated the anti-LSC activity of OTX015 in a niche-like long-term culture in 26 primary AML samples and validated our findings in vivo. OTX015 impaired LSCs in AMLs harbouring Core Binding Factor or KMT2A gene fusions, NPM1 or chromatin/spliceosome genes mutations, but not in those with aneuploidy/TP53 mutations. In four patients, we dissected the transcriptomic footprint of Bet inhibition on LSCs versus blasts. Our results can instruct future clinical trials of BETi in AML.Entities:
Keywords: Acute myeloid leukaemia; BET bromodomains; Leukemic stem cells; Long term culture; MLL partial tandem duplication
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Year: 2019 PMID： 31751766 DOI： 10.1016/j.leukres.2019.106269
Source DB: PubMed Journal: Leuk Res ISSN： 0145-2126 Impact factor: 3.156