Autophagy and the Bone Marrow Microenvironment: A Review of Protective Factors in the Development and Maintenance of Multiple Myeloma

Hamedi, Kamron Reza; Harmon, Katrina A.; Goodwin, Richard L.; Arce, Sergio

doi:10.3389/fimmu.2022.889954

Cited by 5 publications

(5 citation statements)

References 85 publications

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“…Bone marrow microenvironment is a functional network system composed of hematopoietic and non-hematopoietic cells. The pathogenesis of MM affects the relationship between the bone marrow microenvironment and MM cells, promoting the activation of signaling pathways and influencing the survival, development, migration, and drug resistance of MM cells[ 16 ]. This bone marrow invasion leads to anemia, and the weakened immune response can lead to recurrent infections[ 17 ].…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of the efficacy and safety of daratumumab in the treatment of multiple myeloma

Wang,

Jin

2023

World J Clin Cases

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Time series analysis is a valuable tool in epidemiology that complements the classical epidemiological models in two different ways: Prediction and forecast. Prediction is related to explaining past and current data based on various internal and external influences that may or may not have a causative role. Forecasting is an exploration of the possible future values based on the predictive ability of the model and hypothesized future values of the external and/or internal influences. The time series analysis approach has the advantage of being easier to use (in the cases of more straightforward and linear models such as Auto-Regressive Integrated Moving Average). Still, it is limited in forecasting time, unlike the classical models such as Susceptible-Exposed-Infectious-Removed. Its applicability in forecasting comes from its better accuracy for short-term prediction. In its basic form, it does not assume much theoretical knowledge of the mechanisms of spreading and mutating pathogens or the reaction of people and regulatory structures (governments, companies, etc. ). Instead, it estimates from the data directly. Its predictive ability allows testing hypotheses for different factors that positively or negatively contribute to the pandemic spread; be it school closures, emerging variants, etc. It can be used in mortality or hospital risk estimation from new cases, seroprevalence studies, assessing properties of emerging variants, and estimating excess mortality and its relationship with a pandemic.

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Section: Discussionmentioning

confidence: 99%

Meta-analysis of the efficacy and safety of daratumumab in the treatment of multiple myeloma

Wang,

Jin

2023

World J Clin Cases

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“…Autophagy has a controversial role in MM. Thus, it may be an important mechanism driving malignant plasma cell survival and BTZ resistance, but can also mediate cell death [10,29]. To gain insight on the role of autophagy in previously observed phenomena, we analyzed the formation of autophagic vacuoles by flow cytometry.…”

Section: Tig Neutralizes Btz Driven Increased Autophagymentioning

confidence: 99%

“…Mitochondria are also involved in the emergence of BTZ resistance [23][24][25][26][27][28]. Furthermore, BTZ increases autophagy, and its inhibition can antagonize BTZ cytotoxicity [16], suggesting that BTZ could lead to autophagic cell death [29]. Finally, BTZ has been shown to block cell cycle in G2/M phase, inducing apoptosis [22,30].…”

Section: Introductionmentioning

confidence: 99%

Tigecycline Opposes Bortezomib Effect on Myeloma Cells Decreasing Mitochondrial Reactive Oxygen Species Production

Ramos-Acosta,

Huerta-Pantoja,

Salazar-Hidalgo

et al. 2024

IJMS

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Multiple myeloma is an incurable plasma cell malignancy. Most patients end up relapsing and developing resistance to antineoplastic drugs, like bortezomib. Antibiotic tigecycline has activity against myeloma. This study analyzed tigecycline and bortezomib combination on cell lines and plasma cells from myeloma patients. Apoptosis, autophagic vesicles, mitochondrial mass, mitochondrial superoxide, cell cycle, and hydrogen peroxide were studied by flow cytometry. In addition, mitochondrial antioxidants and electron transport chain complexes were quantified by reverse transcription real-time PCR (RT-qPCR) or western blot. Cell metabolism and mitochondrial activity were characterized by Seahorse and RT-qPCR. We found that the addition of tigecycline to bortezomib reduces apoptosis in proportion to tigecycline concentration. Supporting this, the combination of both drugs counteracts bortezomib in vitro individual effects on the cell cycle, reduces autophagy and mitophagy markers, and reverts bortezomib-induced increase in mitochondrial superoxide. Changes in mitochondrial homeostasis and MYC upregulation may account for some of these findings. These data not only advise to avoid considering tigecycline and bortezomib combination for treating myeloma, but caution on the potential adverse impact of treating infections with this antibiotic in myeloma patients under bortezomib treatment.

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“…The emergence of proteasome inhibitors (PIs) and immunomodulatory drugs has significantly developed the prognosis of MM patients. Bortezomib prevents MM cell proliferation, leads to apoptosis, and disturbs MM cell crosstalk with the BM stroma by inhibiting cytokine circuits [ 80 , 81 ]. Even though the efficacy of bortezomib is proven in MM patients, relapse caused by bortezomib resistance is unavoidable, and the malignancy is still untreatable [ 82 ].…”

Section: Multiple Myeloma Drug Resistance and Autophagymentioning

confidence: 99%

Autophagy: A Potential Therapeutic Target to Tackle Drug Resistance in Multiple Myeloma

Bashiri

Tabatabaeian

2023

IJMS

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Multiple myeloma (MM) is the second most prevalent hematologic malignancy. In the past few years, the survival of MM patients has increased due to the emergence of novel drugs and combination therapies. Nevertheless, one of the significant obstacles in treating most MM patients is drug resistance, especially for individuals who have experienced relapses or developed resistance to such cutting-edge treatments. One of the critical processes in developing drug resistance in MM is autophagic activity, an intracellular self-digestive process. Several possible strategies of autophagy involvement in the induction of MM-drug resistance have been demonstrated thus far. In multiple myeloma, it has been shown that High mobility group box protein 1 (HMGB1)-dependent autophagy can contribute to drug resistance. Moreover, activation of autophagy via proteasome suppression induces drug resistance. Additionally, the effectiveness of clarithromycin as a supplemental drug in treating MM has been reported recently, in which autophagy blockage is proposed as one of the potential action mechanisms of CAM. Thus, a promising therapeutic approach that targets autophagy to trigger the death of MM cells and improve drug susceptibility could be considered. In this review, autophagy has been addressed as a survival strategy crucial for drug resistance in MM.

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Autophagy and the Bone Marrow Microenvironment: A Review of Protective Factors in the Development and Maintenance of Multiple Myeloma

Cited by 5 publications

References 85 publications

Meta-analysis of the efficacy and safety of daratumumab in the treatment of multiple myeloma

Meta-analysis of the efficacy and safety of daratumumab in the treatment of multiple myeloma

Tigecycline Opposes Bortezomib Effect on Myeloma Cells Decreasing Mitochondrial Reactive Oxygen Species Production

Autophagy: A Potential Therapeutic Target to Tackle Drug Resistance in Multiple Myeloma

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