RT Journal Article
T1 Pathogenetic and Prognostic Implications of Increased Mitochondrial Content in Multiple Myeloma
A1 Ruiz Heredia, Yanira
A1 Ortiz Ruiz, Alejandra
A1 Samur, Mehmet K.
A1 Garrido, Vanesa
A1 Rufian, Laura
A1 Sanchez, Ricardo
A1 Aguilar-Garrido, Pedro
A1 Barrio, Santiago
A1 Martín, Miguel A.
A1 Bolli, Niccolò
A1 Tai, Yu-Tzu
A1 Szalat, Raphaël
A1 Fulciniti, Mariateresa
A1 Munshi, Nikhil
A1 Martínez López, Joaquín
A1 Linares Gómez, María
A1 Gallardo, Miguel
AB Many studies over the last 20 years have investigated the role of mitochondrial DNA (mtDNA) alterations in carcinogenesis. However, the status of the mtDNACN in MM and its implication in the pathogenesis of the disease remains unclear. We examined changes in plasma cell mtDNACN across different stages of MM by applying RT-PCR and high-throughput sequencing analysis. We observed a significant increase in the average mtDNACN in myeloma cells compared with healthy plasma cells (157 vs. 40 copies; p = 0.02). We also found an increase in mtDNACN in SMM and newly diagnosed MM (NDMM) paired samples and in consecutive relapses in the same patient. Survival analysis revealed the negative impact of a high mtDNACN in progression-free survival in NDMM (p = 0.005). Additionally, we confirmed the higher expression of mitochondrial biogenesis regulator genes in myeloma cells than in healthy plasma cells and we detected single nucleotide variants in several genes involved in mtDNA replication. Finally, we found that there was molecular similarity between “rapidly-progressing SMM” and MM regarding mtDNACN. Our data provide evidence that malignant transformation of myeloma cells involves the activation of mitochondrial biogenesis, resulting in increased mtDNA levels, and highlights vulnerabilities and potential therapeutic targets in the treatment of MM. Accordingly, mtDNACN tracking might guide clinical decision-making and management of complex entities such as high-risk SMM.
PB MPDI
SN 2072-6694
YR 2021
FD 2021-06-25
LK https://hdl.handle.net/20.500.14352/6878
UL https://hdl.handle.net/20.500.14352/6878
LA eng
NO Unión Europea. Horizonte 2020
NO Instituto de Salud Carlos III (ISCIII)
NO Comunidad de Madrid
NO Fundación contra el Cancer, CRIS, Miguel Servet
NO AECC
DS Docta Complutense
RD 19 abr 2025