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Di Lernia G, Leone P, Solimando AG, et al. Bortezomib Treatment Modulates Autophagy in Multiple Myeloma. J Clin Med. 2020;9(2)doi: 10.3390/jcm9020552.
Di Lernia, G., Leone, P., Solimando, A. G., Buonavoglia, A., Saltarella, I., Ria, R., Ditonno, P., Silvestris, N., Crudele, L., Vacca, A., & Racanelli, V. (2020). Bortezomib Treatment Modulates Autophagy in Multiple Myeloma. Journal of clinical medicine, 9(2), . https://doi.org/10.3390/jcm9020552
Di Lernia, Giuseppe, et al. "Bortezomib Treatment Modulates Autophagy in Multiple Myeloma." Journal of clinical medicine vol. 9,2 (2020). doi: https://doi.org/10.3390/jcm9020552
Di Lernia G, Leone P, Solimando AG, Buonavoglia A, Saltarella I, Ria R, Ditonno P, Silvestris N, Crudele L, Vacca A, Racanelli V. Bortezomib Treatment Modulates Autophagy in Multiple Myeloma. J Clin Med. 2020 Feb 18;9(2). doi: 10.3390/jcm9020552. PMID: 32085480; PMCID: PMC7073518.
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J Clin Med. 2020 Feb 18;9(2). doi: 10.3390/jcm9020552.

Bortezomib Treatment Modulates Autophagy in Multiple Myeloma.

Journal of clinical medicine

Giuseppe Di Lernia, Patrizia Leone, Antonio Giovanni Solimando, Alessio Buonavoglia, Ilaria Saltarella, Roberto Ria, Paolo Ditonno, Nicola Silvestris, Lucilla Crudele, Angelo Vacca, Vito Racanelli

Affiliations

  1. Department of Biomedical Sciences and Human Oncology, Unit of Internal Medicine "Guido Baccelli", University of Bari Medical School, 70124 Bari, Italy.
  2. IRCCS Istituto Tumori "Giovanni Paolo II", 70124 Bari, Italy.

PMID: 32085480 PMCID: PMC7073518 DOI: 10.3390/jcm9020552

Abstract

Although the introduction of bortezomib as a therapeutic strategy has improved the overall survival of multiple myeloma (MM) patients, 15-20% of high-risk patients do not respond to bortezomib over time or become resistant to treatment. Therefore, the development of new therapeutic strategies, such as combination therapies, is urgently needed.

METHODS: Given that bortezomib resistance may be mediated by activation of the autophagy pathway as an alternative mechanism of protein degradation, and that an enormous amounts of misfolded protein is generated in myeloma plasma cells (PCs), we investigated the effect of the simultaneous inhibition of proteasome by bortezomib and autophagy by hydroxychloroquine (HCQ) treatment on PCs and endothelial cells (ECs) isolated from patients with monoclonal gammopathy of undetermined significance (MGUS) and MM.

RESULTS: We found that bortezomib combined with HCQ induces synergistic cytotoxicity in myeloma PCs whereas this effect is lost on ECs. Levels of microtubule-associated protein light chain beta (LC3B) and p62 are differentially modulated in PCs and ECs, with effects on cell viability and proliferation.

CONCLUSIONS: Our results suggest that treatment with bortezomib and HCQ should be associated with an anti-angiogenic drug to prevent the pro-angiogenic effect of bortezomib, the proliferation of a small residual tumor PC clone, and thus the relapse.

Keywords: angiogenesis; autophagy; bortezomib; drug resistance; endothelial cells; multiple myeloma; plasma cells

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