Myeloma Bone Disease: The Osteoblast in the Spotlight

Andrews, Rebecca E.; Brown, Janet; Lawson, Michelle A.; Chantry, Andrew

doi:10.3390/jcm10173973

Cited by 8 publications

(12 citation statements)

References 111 publications

(134 reference statements)

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“…It has been shown that CD38 is expressed by effectors and inhibitory cells and by osteoblasts. CD38 also appears to be involved in the formation and differentiation of osteoclasts and may play a role in bone remodeling [ 86 , 87 ]. Hence, there is a rationale for using the anti-CD38 monoclonal antibody (Daratumumab) against MM bone disease and the protection of MM PCs by BMSCs [ 86 , 87 , 88 ].…”

Section: Cytokines and Bone Resorptionmentioning

confidence: 99%

Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance

Melaccio

Reale

Saltarella

et al. 2022

JCM

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Multiple myeloma (MM) is the second most common hematological malignancy, and despite the introduction of innovative therapies, remains an incurable disease. Identifying early and minimally or non-invasive biomarkers for predicting clinical outcomes and therapeutic responses is an active field of investigation. Malignant plasma cells (PCs) reside in the bone marrow (BM) microenvironment (BMME) which comprises cells (e.g., tumour, immune, stromal cells), components of the extracellular matrix (ECM) and vesicular and non-vesicular (soluble) molecules, all factors that support PCs’ survival and proliferation. The interaction between PCs and BM stromal cells (BMSCs), a hallmark of MM progression, is based not only on intercellular interactions but also on autocrine and paracrine circuits mediated by soluble or vesicular components. In fact, PCs and BMSCs secrete various cytokines, including angiogenic cytokines, essential for the formation of specialized niches called “osteoblastic and vascular niches”, thus supporting neovascularization and bone disease, vital processes that modulate the pathophysiological PCs–BMME interactions, and ultimately promoting disease progression. Here, we aim to discuss the roles of cytokines and growth factors in pathogenetic pathways in MM and as prognostic and predictive biomarkers. We also discuss the potential of targeted drugs that simultaneously block PCs’ proliferation and survival, PCs–BMSCs interactions and BMSCs activity, which may represent the future goal of MM therapy.

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Section: Cytokines and Bone Resorptionmentioning

confidence: 99%

Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance

Melaccio

Reale

Saltarella

et al. 2022

JCM

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“…In the study by Wang et al (2014), gambogic acid treatment suppressed MM progression and angiogenesis through inhibition of HIF1α/VEGF expression, which was associated with the inhibition of PI3K/Akt/ mTOR pathway. Osteoporosis and lytic lesions are also common in patients with MM (Andrews et al, 2021). Stromal cell-derived factor 1α (SDF-1α)/CXC chemokine receptor 4 (CXCR4) signaling has been shown to be associated with osteoclastogenesis (Dong et al, 2016).…”

Section: Gambogic Acidmentioning

confidence: 99%

Active Components of Traditional Chinese Medicinal Material for Multiple Myeloma: Current Evidence and Future Directions

Cheng

et al. 2022

Front. Pharmacol.

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Multiple myeloma (MM) is a hematological malignancy characterized by clonal expansion of plasma cells in bone marrow, leading to the overproduction of monoclonal immunoglobulins. The clinical manifestations resulting from monoclonal proteins and malignant cells include signs of end-organ damage, such as hypercalcemia, renal failure, anemia, and bone lesions. Despite improvement in the survival of MM patients with use of myeloma-targeted and immunomodulatory therapies, MM remains an incurable disease. Moreover, patients with relapsed or refractory MM show poor survival outcomes. In recent years, there has been a growing interest in the use of traditional Chinese medicinal materials (TCMMs) for management of a wide spectrum of diseases. The bioactive ingredients derived from TCMMs hold great potential for the development of anticancer drugs. Here we summarize the evidence of the pharmacological effects of the active components in TCMMs on MM, including curcumin, resveratrol, baicalein, berberine, bufalin, cinobufagin, gambogic acid, ginsenoside, icariin, daidzin, formononetin, polysaccharides extracts from Hedyotis difus, and scutellarein. Available evidence indicates that the anti-MM effects of these bioactive ingredients are mediated via regulation of proliferation, apoptosis, autophagy, cell cycle, osteogenic differentiation, and drug resistance. In the future, the underlying mechanisms of the anti-MM effects of these components should be further investigated. Large-scale and well-designed clinical trials are also required to validate the efficacy of these bioactive constituents for MM.

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“…Simultaneously, myeloma cells inhibit osteoblast formation, thereby preventing formation of new bone and exacerbating the impact of the osteolytic bone disease. The vicious cycle and the many factors that stimulate osteoclasts and inhibit osteoblasts have been described previously in a number of reviews (26)(27)(28)(29).…”

Section: Myeloma Pathogenesis and Bone Diseasementioning

confidence: 99%

“…The pathogenesis of myeloma is facilitated by the direct and indirect interactions between myeloma cells and microenvironment cells ( 26 – 29 ). Of particular relevance to the development of myeloma bone disease and control of myeloma dormancy are osteoclasts, osteoblasts and bone lining cells ( 19 , 26 , 29 – 31 ).…”

Section: Myeloma Pathogenesis and Bone Diseasementioning

confidence: 99%

Section: Myeloma Pathogenesis and Bone Diseasementioning

confidence: 99%

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The role of the bone microenvironment in regulating myeloma residual disease and treatment

Dadzie

Green

2022

Front. Oncol.

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Multiple myeloma is an incurable haematological cancer. The increase in targeted therapies has improved the number of myeloma patients achieving a complete response and improved progression-free survival following therapy. However, a low level of disease or minimal residual disease (MRD) still persists which contributes to the inevitable relapse in myeloma patients. MRD has been attributed to the presence of dormant myeloma cells and their subsequent reactivation, which is controlled by the microenvironment and specialised niches within the bone marrow. This contributes to the evasion of the immune system and chemotherapy, eventually leading to relapse. The growth of myeloma tumours are heavily dependent on environmental stimuli from the bone marrow microenvironment, and this plays a key role in myeloma progression. The bone microenvironment also plays a critical role in myeloma bone disease and the development of skeletal-related events. This review focuses on the bone marrow microenvironment in relation to myeloma pathogenesis and cancer dormancy. Moreover, it reviews the current therapies targeting the bone microenvironment to treat myeloma and myeloma bone disease. Lastly, it identifies novel therapeutic targets for myeloma treatment and the associated bone disease.

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Myeloma Bone Disease: The Osteoblast in the Spotlight

Cited by 8 publications

References 111 publications

Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance

Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance

Active Components of Traditional Chinese Medicinal Material for Multiple Myeloma: Current Evidence and Future Directions

The role of the bone microenvironment in regulating myeloma residual disease and treatment

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