000162989 001__ 162989
000162989 005__ 20251009133840.0
000162989 0247_ $$2doi$$a10.3390/cells14171343
000162989 0248_ $$2sideral$$a145547
000162989 037__ $$aART-2025-145547
000162989 041__ $$aeng
000162989 100__ $$aMarco-Brualla, Joaquín
000162989 245__ $$aThe Combination of Ibrutinib with BH3 Mimetics or Dichloroacetate Is Effective in B-CLL
000162989 260__ $$c2025
000162989 5060_ $$aAccess copy available to the general public$$fUnrestricted
000162989 5203_ $$aSince its discovery, the BTK inhibitor ibrutinib has redefined the standard treatments for hematological cancers, such as chronic lymphocytic leukemia (CLL). However, concerns exist regarding its secondary effects in humans and its occasional lack of efficacy in certain malignancies. Therefore, combined therapies with ibrutinib have emerged as promising new approaches. In this study, we aimed to explore its therapeutic potential through different approaches. For this purpose, we combined this drug with the BH3 mimetics ABT-199 and ABT-737, which inhibit anti-apoptotic members of the Bcl-2 family, and with the PDK1 inhibitor dichloroacetate (DCA), respectively. As cell models, we used ex vivo samples from patients and also selected the in vitro CLL cell line Mec-1, generating two sub-lines overexpressing Bcl-XL and Mcl-1, a common feature in this cancer. Results demonstrated a synergistic effect for both approaches, in all tumor cells tested, for both cytostatic and cytotoxic effects. Mechanistically, the expression of Bcl-2-family proteins was explored, exhibiting increases in pro-apoptotic, but also in anti-apoptotic, proteins upon ibrutinib treatment and a relative increase in the amount of the pro-apoptotic protein PUMA after treatment with DCA. Our data provides new insights into combined therapies with ibrutinib for CLL, which further expands our knowledge and the potential of this drug for cancer treatment.
000162989 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B31-20R$$9info:eu-repo/grantAgreement/ES/DGA/B23-20R$$9info:eu-repo/grantAgreement/ES/MICINN/PID2019-105128RB-I00$$9info:eu-repo/grantAgreement/ES/MICINN/PID2022-136799OB-I00
000162989 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttps://creativecommons.org/licenses/by/4.0/deed.es
000162989 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000162989 700__ $$0(orcid)0000-0002-7444-2341$$aGonzalo, Oscar
000162989 700__ $$0(orcid)0000-0001-5068-7355$$aAzaceta, Gemma$$uUniversidad de Zaragoza
000162989 700__ $$aIzquierdo, Isabel$$uUniversidad de Zaragoza
000162989 700__ $$0(orcid)0000-0001-8515-3599$$aPalomera, Luis
000162989 700__ $$aVillalba, Martín
000162989 700__ $$0(orcid)0000-0002-2315-9079$$aMarzo, Isabel$$uUniversidad de Zaragoza
000162989 700__ $$0(orcid)0000-0002-5175-8394$$aAnel, Alberto$$uUniversidad de Zaragoza
000162989 7102_ $$11007$$2610$$aUniversidad de Zaragoza$$bDpto. Medicina, Psiqu. y Derm.$$cArea Medicina
000162989 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000162989 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000162989 773__ $$g14, 17 (2025), 1343 [18 pp.]$$pCells$$tCells$$x2073-4409
000162989 8564_ $$s3050845$$uhttps://zaguan.unizar.es/record/162989/files/texto_completo.pdf$$yVersión publicada
000162989 8564_ $$s2488563$$uhttps://zaguan.unizar.es/record/162989/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000162989 909CO $$ooai:zaguan.unizar.es:162989$$particulos$$pdriver
000162989 951__ $$a2025-10-09-13:25:52
000162989 980__ $$aARTICLE