Myc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma



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Ortiz Ruiz, Alejandra and Ruiz Heredia, Yanira and Morales, María Luz and Aguilar Garrido, Pedro and García Ortiz, Almudena and Valeri Lozano, Antonio and Bárcena Asensio, Carmen and García Martín, Rosa María and Garrido, Vanesa and Moreno Gutiérrez, Laura and Gimenez, Alicia and Navarro Aguadero, Miguel Ángel and Velasco Estévez, María and Lospitao, Eva and Cedena, María Teresa and Barrio, Santiago and Martínez López, Joaquín and Linares Gómez, María and Gallardo, Miguel (2021) Myc-Related Mitochondrial Activity as a Novel Target for Multiple Myeloma. Cancers, 13 (7). p. 1662. ISSN 2072-6694

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Mitochondria are involved in the development and acquisition of a malignant phenotype in hematological cancers. Recently, their role in the pathogenesis of multiple myeloma (MM) has been suggested to be therapeutically explored. MYC is a master regulator of b-cell malignancies such as multiple myeloma, and its activation is known to deregulate mitochondrial function. We investigated the impact of mitochondrial activity on the distinct entities of the disease and tested the efficacy of the mitochondrial inhibitor, tigecycline, to overcome MM proliferation. COXII expression, COX activity, mitochondrial mass, and mitochondrial membrane potential demonstrated a progressive increase of mitochondrial features as the disease progresses. In vitro and in vivo therapeutic targeting using the mitochondrial inhibitor tigecycline showed promising efficacy and cytotoxicity in monotherapy and combination with the MM frontline treatment bortezomib. Overall, our findings demonstrate how mitochondrial activity emerges in MM transformation and disease progression and the efficacy of therapies targeting these novel vulnerabilities.

Item Type:Article
Uncontrolled Keywords:multiple myeloma; mitochondria; tigecycline; MYC
Subjects:Medical sciences > Medicine > Hematology
Medical sciences > Medicine > Oncology
Medical sciences > Biology > Cytology
ID Code:70922
Deposited On:02 Mar 2022 15:17
Last Modified:03 Mar 2022 09:03

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