000095959 001__ 95959
000095959 005__ 20210121114527.0
000095959 0247_ $$2doi$$a10.1016/j.celrep.2015.12.003
000095959 0248_ $$2sideral$$a116939
000095959 037__ $$aART-2015-116939
000095959 041__ $$aeng
000095959 100__ $$aBenito, Juliana M.
000095959 245__ $$aMLL-Rearranged Acute Lymphoblastic Leukemias Activate BCL-2 through H3K79 Methylation and Are Sensitive to the BCL-2-Specific Antagonist ABT-199
000095959 260__ $$c2015
000095959 5060_ $$aAccess copy available to the general public$$fUnrestricted
000095959 5203_ $$aTargeted therapies designed to exploit specific molecular pathways in aggressive cancers are an exciting area of current research. Mixed Lineage Leukemia (MLL) mutations such as the t(4;11) translocation cause aggressive leukemias that are refractory to conventional treatment. The t(4;11) translocation produces an MLL/AF4 fusion protein that activates key target genes through both epigenetic and transcriptional elongation mechanisms. In this study, we show that t(4;11) patient cells express high levels of BCL-2 and are highly sensitive to treatment with the BCL-2-specific BH3 mimetic ABT-199. We demonstrate that MLL/AF4 specifically upregulates the BCL-2 gene but not other BCL-2 family members via DOT1L-mediated H3K79me2/3. We use this information to show that a t(4;11) cell line is sensitive to a combination of ABT-199 and DOT1L inhibitors. In addition, ABT-199 synergizes with standard induction-type therapy in a xenotransplant model, advocating for the introduction of ABT-199 into therapeutic regimens for MLL-rearranged leukemias. Therapies designed to exploit specific molecular pathways in aggressive cancers are an exciting area of research. Mutations in the MLL gene cause aggressive incurable leukemias. Benito et al. show that MLL leukemias are highly sensitive to BCL-2 inhibitors, especially when combined with drugs that target mutant MLL complex activity.
000095959 540__ $$9info:eu-repo/semantics/openAccess$$aby-nc-nd$$uhttp://creativecommons.org/licenses/by-nc-nd/3.0/es/
000095959 590__ $$a7.87$$b2015
000095959 591__ $$aCELL BIOLOGY$$b26 / 187 = 0.139$$c2015$$dQ1$$eT1
000095959 592__ $$a8.545$$b2015
000095959 593__ $$aBiochemistry, Genetics and Molecular Biology (miscellaneous)$$c2015$$dQ1
000095959 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000095959 700__ $$aGodfrey, Laura
000095959 700__ $$aKojima, Kensuke
000095959 700__ $$aHogdal, Leah
000095959 700__ $$aWunderlich, Mark
000095959 700__ $$aGeng, Huimin
000095959 700__ $$0(orcid)0000-0002-2315-9079$$aMarzo, Isabel$$uUniversidad de Zaragoza
000095959 700__ $$aHarutyunyan, Karine G.
000095959 700__ $$aGolfman, Leonard
000095959 700__ $$aNorth, Phillip
000095959 700__ $$aKerry, Jon
000095959 700__ $$aBallabio, Erica
000095959 700__ $$aChonghaile, Triona Ní
000095959 700__ $$aGonzalo, Oscar
000095959 700__ $$aQiu, Yihua
000095959 700__ $$aJeremias, Irmela
000095959 700__ $$aDebose, LaKiesha
000095959 700__ $$aO\u2019Brien, Eric
000095959 700__ $$aMa, Helen
000095959 700__ $$aZhou, Ping
000095959 700__ $$aJacamo, Rodrigo
000095959 700__ $$aPark, Eugene
000095959 700__ $$aCoombes, Kevin R.
000095959 700__ $$aZhang, Nianxiang
000095959 700__ $$aThomas, Deborah A.
000095959 700__ $$aO\u2019Brien, Susan
000095959 700__ $$aKantarjian, Hagop M.
000095959 700__ $$aLeverson, Joel D.
000095959 700__ $$aKornblau, Steven M.
000095959 700__ $$aAndreeff, Michael
000095959 700__ $$aMüschen, Markus
000095959 700__ $$aZweidler-McKay, Patrick A.
000095959 700__ $$aMulloy, James C.
000095959 700__ $$aLetai, Anthony
000095959 700__ $$aMilne, Thomas A.
000095959 700__ $$aKonopleva, Marina
000095959 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000095959 773__ $$g13, 12 (2015), 2715-2727$$pCell Reports$$tCell Reports$$x2211-1247
000095959 8564_ $$s1744696$$uhttps://zaguan.unizar.es/record/95959/files/texto_completo.pdf$$yVersión publicada
000095959 8564_ $$s41919$$uhttps://zaguan.unizar.es/record/95959/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000095959 909CO $$ooai:zaguan.unizar.es:95959$$particulos$$pdriver
000095959 951__ $$a2021-01-21-11:07:29
000095959 980__ $$aARTICLE