Myeloma and marrow adiposity: Unanswered questions and future directions

Morris, Emma V.; Edwards, Claire

doi:10.1016/j.beem.2021.101541

Cited by 4 publications

(6 citation statements)

References 65 publications

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“…In addition to the above, obesity increases the number and size of bone marrow adipocytes [ 117 ]. Accumulating evidence has shown that adipocytes are in close interplay with myeloma cells [ 117 , 118 ]. Bone marrow adipocytes have a dual role; being an energy depository andinvolvement in metabolic activity by providing adipokines and bioactive molecules [ 118 ].…”

Section: Metabolic Syndromementioning

confidence: 99%

“…Accumulating evidence has shown that adipocytes are in close interplay with myeloma cells [ 117 , 118 ]. Bone marrow adipocytes have a dual role; being an energy depository andinvolvement in metabolic activity by providing adipokines and bioactive molecules [ 118 ]. Myeloma cells may regulate adipogenesis in order to sustain their survival and homing in the bone marrow milieu [ 118 ].…”

Section: Metabolic Syndromementioning

confidence: 99%

“…Bone marrow adipocytes have a dual role; being an energy depository andinvolvement in metabolic activity by providing adipokines and bioactive molecules [ 118 ]. Myeloma cells may regulate adipogenesis in order to sustain their survival and homing in the bone marrow milieu [ 118 ]. Myeloma cells induce the expression of genes related to an inflammatory state and a senescence associated secretory phenotype (SAPS) in the adipocytes, in order to promote myelomatogenesis and myeloma cell survival [ 119 ].…”

Section: Metabolic Syndromementioning

confidence: 99%

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Metabolic Disorders in Multiple Myeloma

Gavriatopoulou

Paschou

Ntanasis‐Stathopoulos

et al. 2021

IJMS

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Multiple myeloma (MM) is the second most common hematological malignancy and is attributed to monoclonal proliferation of plasma cells in the bone marrow. Cancer cells including myeloma cells deregulate metabolic pathways to ensure proliferation, growth, survival and avoid immune surveillance, with glycolysis and glutaminolysis being the most identified procedures involved. These disorders are considered a hallmark of cancer and the alterations performed ensure that enough energy is available for rapid cell proliferation. An association between metabolic syndrome, inflammatory cytokinesand incidence of MM has been also described, while the use of metformin and statins has been identified as a positive prognostic factor for the disease course. In this review, we aim to present the metabolic disorders that occur in multiple myeloma, the potential defects on the immune system and the potential advantage of targeting the dysregulated pathways in order to enhance antitumor therapeutics.

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Section: Metabolic Syndromementioning

confidence: 99%

Section: Metabolic Syndromementioning

confidence: 99%

Section: Metabolic Syndromementioning

confidence: 99%

See 1 more Smart Citation

Metabolic Disorders in Multiple Myeloma

Gavriatopoulou

Paschou

Ntanasis‐Stathopoulos

et al. 2021

IJMS

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“…226 Moreover, cell-cell contact with adipocytes is critical for supporting myeloma cells through numerous adipokines. 227 (Fig. 6.2).…”

Section: Skeletal Aging and The Bone Marrow Microenvironmentmentioning

confidence: 98%

The roles of bone remodeling in normal hematopoiesis and age-related hematological malignancies

et al. 2023

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Prior research establishing that bone interacts in coordination with the bone marrow microenvironment (BMME) to regulate hematopoietic homeostasis was largely based on analyses of individual bone-associated cell populations. Recent advances in intravital imaging has suggested that the expansion of hematopoietic stem cells (HSCs) and acute myeloid leukemia cells is restricted to bone marrow microdomains during a distinct stage of bone remodeling. These findings indicate that dynamic bone remodeling likely imposes additional heterogeneity within the BMME to yield differential clonal responses. A holistic understanding of the role of bone remodeling in regulating the stem cell niche and how these interactions are altered in age-related hematological malignancies will be critical to the development of novel interventions. To advance this understanding, herein, we provide a synopsis of the cellular and molecular constituents that participate in bone turnover and their known connections to the hematopoietic compartment. Specifically, we elaborate on the coupling between bone remodeling and the BMME in homeostasis and age-related hematological malignancies and after treatment with bone-targeting approaches. We then discuss unresolved questions and ambiguities that remain in the field.

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“…The bone marrow microenvironment plays an important role in MM progression and bone disease. With age and obesity, there is a significant increase in the proportion of bone marrow adipocytes; these cells provide an energy store, adipokines and bioactive substances, that MM cells utilize for migration, growth and survival 32 . BMAT is also supportive of OC formation 33 .…”

Section: Eliglustat Inhibits Osteoclastogenesis Leading To a Decrease...mentioning

confidence: 99%

Modulating glycosphingolipid metabolism and autophagy improves outcomes in pre-clinical models of myeloma bone disease

Leng

Zhang

et al. 2022

Nat Commun

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Patients with multiple myeloma, an incurable malignancy of plasma cells, frequently develop osteolytic bone lesions that severely impact quality of life and clinical outcomes. Eliglustat, a U.S. Food and Drug Administration-approved glucosylceramide synthase inhibitor, reduced osteoclast-driven bone loss in preclinical in vivo models of myeloma. In combination with zoledronic acid, a bisphosphonate that treats myeloma bone disease, eliglustat provided further protection from bone loss. Autophagic degradation of TRAF3, a key step for osteoclast differentiation, was inhibited by eliglustat as evidenced by TRAF3 lysosomal and cytoplasmic accumulation. Eliglustat blocked autophagy by altering glycosphingolipid composition whilst restoration of missing glycosphingolipids rescued autophagy markers and TRAF3 degradation thus restoring osteoclastogenesis in bone marrow cells from myeloma patients. This work delineates both the mechanism by which glucosylceramide synthase inhibition prevents autophagic degradation of TRAF3 to reduce osteoclastogenesis as well as highlighting the clinical translational potential of eliglustat for the treatment of myeloma bone disease.

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Myeloma and marrow adiposity: Unanswered questions and future directions

Cited by 4 publications

References 65 publications

Metabolic Disorders in Multiple Myeloma

Metabolic Disorders in Multiple Myeloma

The roles of bone remodeling in normal hematopoiesis and age-related hematological malignancies

Modulating glycosphingolipid metabolism and autophagy improves outcomes in pre-clinical models of myeloma bone disease

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