Alteration of mitochondrial biogenesis promotes disease progression in multiple myeloma

Zhan, Xin; Yu, Wenjie; Franqui-Machin, Reinaldo; Bates, Melissa L.; Nadiminti, Kalyan; Cao, Huojun; Amendt, Brad A.; Jethava, Yogesh; Frech, Ivana; Zhan, Fenghuang; Tricot, Guido

doi:10.18632/oncotarget.22740

Cited by 41 publications

(31 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, Zhan et al demonstrated that gene expression of mitochondrial biogenesis signatures were significantly higher in relapsed and drug resistant myeloma samples than newly diagnosed patient samples. Inhibition of mitochondria OXPHOS dramatically reduced the growth of MM xenograft in in vivo model [168]. Similar results were reported by Alejandra Ortiz-Ruiz and colleagues [169].…”

Section: The Role Of Nrf2 In Mitochondrial Regulation In Myelomasupporting

confidence: 85%

Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2

Yen

Hsu

Hsiao

et al. 2020

IJMS

View full text Add to dashboard Cite

Osteolytic bone lesions are one of the central features of multiple myeloma (MM) and lead to bone pain, fractures, decreased quality of life, and decreased survival. Dysfunction of the osteoclast (OC)/osteoblast (OB) axis plays a key role in the development of myeloma-associated osteolytic lesions. Many signaling pathways and factors are associated with myeloma bone diseases (MBDs), including the RANKL/OPG and NF-κB pathways. NRF2, a master regulator of inflammatory signaling, might play a role in the regulation of bone metabolism via anti-inflammatory signaling and decreased reactive oxygen species (ROS) levels. The loss of NRF2 expression in OCs reduced bone mass via the RANK/RANKL pathway and other downstream signaling pathways that affect osteoclastogenesis. The NRF2 level in OBs could interfere with interleukin (IL)-6 expression, which is associated with bone metabolism and myeloma cells. In addition to direct impact on OCs and OBs, the activity of NRF2 on myeloma cells and mesenchymal stromal cells influences the inflammatory stress/ROS level in these cells, which has an impact on OCs, OBs, and osteocytes. The interaction between these cells and OCs affects the osteoclastogenesis of myeloma bone lesions associated with NRF2. Therefore, we have reviewed the effects of NRF2 on OCs and OBs in MBDs.

show abstract

Section: The Role Of Nrf2 In Mitochondrial Regulation In Myelomasupporting

confidence: 85%

Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2

Yen

Hsu

Hsiao

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…In relapsed and refractory patients MM PCs overexpress mitochondrial biogenesis signatures regulated by the cellular iron content ( 133 ). The consequent loss of integrity of redox balance, with the nuclear compartmentalization of heme-oxygenase 1 is associated to drug resistance and genomic instability ( 134 ).…”

Section: Mitochondrial Fitness Mediates Resistance To Bortezomib In Mmentioning

confidence: 99%

Mitochondrial Bioenergetics at the Onset of Drug Resistance in Hematological Malignancies: An Overview

et al. 2020

View full text Add to dashboard Cite

The combined derangements in mitochondria network, function and dynamics can affect metabolism and ATP production, redox homeostasis and apoptosis triggering, contributing to cancer development in many different complex ways. In hematological malignancies, there is a strong relationship between cellular metabolism, mitochondrial bioenergetics, interconnections with supportive microenvironment and drug resistance. Lymphoma and chronic lymphocytic leukemia cells, e.g., adapt to intrinsic oxidative stress by increasing mitochondrial biogenesis. In other hematological disorders such as myeloma, on the contrary, bioenergetics changes, associated to increased mitochondrial fitness, derive from the adaptive response to drug-induced stress. In the bone marrow niche, a reverse Warburg effect has been recently described, consisting in metabolic changes occurring in stromal cells in the attempt to metabolically support adjacent cancer cells. Moreover, a physiological dynamic, based on mitochondria transfer, between tumor cells and their supporting stromal microenvironment has been described to sustain oxidative stress associated to proteostasis maintenance in multiple myeloma and leukemia. Increased mitochondrial biogenesis of tumor cells associated to acquisition of new mitochondria transferred by mesenchymal stromal cells results in augmented ATP production through increased oxidative phosphorylation (OX-PHOS), higher drug resistance, and resurgence after treatment. Accordingly, targeting mitochondrial biogenesis, electron transfer, mitochondrial DNA replication, or mitochondrial fatty acid transport increases therapy efficacy. In this review, we summarize selected examples of the mitochondrial derangements in hematological malignancies, which provide metabolic adaptation and apoptosis resistance, also supported by the crosstalk with tumor microenvironment. This field promises a rational design to improve target-therapy including the metabolic phenotype.

show abstract

“…As far as the case described by Antonucci et al (2019b) is concerned, it is worth considering that this neoplasia is among those that accumulate iron, a metal essential to promote cancer cell growth and resistance to chemotherapy. High levels of iron in the cytosol react with ROS produced by defective mitochondria in cancer cells and this leads to further oxidative damage (Zhan et al, 2017). It is therefore plausible that the encouraging results reported by (Antonucci et al, 2019b) may be ascribed also to the restoration of mitochondrial functionality associated with detoxification of metals as also described in (Blythe et al, 2017).…”

Section: Resultsmentioning

confidence: 82%

Color Doppler Evaluation of Isovolumetric Relaxation Time and of Signals Arising from Axons of the Median Nerve as a Means to Evaluate Mitochondrial Functionality in the Context of Immunotherapy of Cancer and Chronic Conditions Associated with Mitochondrial Dysfunction

Pacini¹,

Ruggiero²

2019

American Journal of Immunology

View full text Add to dashboard Cite

Reactive Oxygen Species (ROS) arising from the disruption of mitochondrial respiration act as endogenous mutagens and tumor promoters. When production of ROS exceeds the capacity of DNA repair mechanisms, random mutations and aneuploidy ensue, thousands of genes become unbalanced and genetic/epigenetic chain reactions lead to progressive aneuploidy with only two outcomes: karyotypes so altered that are not viable or karyotypes of autonomous, immortal, cancer cells. Consistent with the concept that abnormalities of cellular respiration in mitochondria precede DNA alterations in the nucleus, transplant of normal mitochondria suppresses tumorigenesis and metastases in vitro and in vivo. However, the transplant of mitochondria is an experimental procedure that cannot be easily applied to clinical practice. In order to overcome this limitation, we designed a novel formula based on microbial chondroitin sulfate, vitamin D3 and ultrapure phosphatidylcholine, molecules that are known to restore mitochondrial functionality and suppress ROS production. Here we describe how such an approach can be evaluated by color Doppler ultrasonography of the radial artery and measure of the Isovolumetric Relaxation Time (IVRT). In addition, we show for the first time color Doppler signals originating from axons of the median nerve that may be indicative of quantum phenomena at the level of mitochondria. We propose the use of the original ultrasonographic techniques here described for evaluating the effectiveness of substances or strategies aimed at restoring mitochondrial functionality at the macroscopic and quantum levels.

show abstract

Alteration of mitochondrial biogenesis promotes disease progression in multiple myeloma

Cited by 41 publications

References 38 publications

Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2

Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2

Mitochondrial Bioenergetics at the Onset of Drug Resistance in Hematological Malignancies: An Overview

Color Doppler Evaluation of Isovolumetric Relaxation Time and of Signals Arising from Axons of the Median Nerve as a Means to Evaluate Mitochondrial Functionality in the Context of Immunotherapy of Cancer and Chronic Conditions Associated with Mitochondrial Dysfunction

Contact Info

Product

Resources

About