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Cited by 10Multiple Myeloma Research and TreatmentsCancer, Hypoxia, and MetabolismBone health and treatments

Metabolic features of myeloma cells in the context of bone microenvironment: Implication for the pathophysiology and clinic of myeloma bone disease

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Raimondi, Vincenzo, Toscani, Denise, Marchica, Valentina, Burroughs-Garcia, Jessica, Storti, Paola, Giuliani, Nicola·2022·Frontiers in Oncology
DOI 10.3389/fonc.2022.1015402PMC PMC9608343
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Abstract

Multiple myeloma (MM) is a hematological malignancy characterized by the accumulation of malignant plasma cells (PCs) into the bone marrow (BM). The complex interaction between the BM microenvironment and MM PCs can lead to severe impairment of bone remodeling. Indeed, the BM microenvironment exerts a critical role in the survival of malignant PCs. Growing evidence indicates that MM cells have several metabolic features including enhanced glycolysis and an increase in lactate production through the upregulation of glucose transporters and enzymes. More recently, it has been reported that MM cells arehighly glutamine addicted. Interestingly, these metabolic changes in MM cells may affect BM microenvironment cells by altering the differentiation process of osteoblasts from mesenchymal stromal cells. The identification of glutamine metabolism alterations in MM cells and bone microenvironment may provide a rationale to design new therapeutic approaches and diagnostic tools. The osteolytic lesions are the most frequent clinical features in MM patients, often characterized by pathological fractures and acute pain. The use of the newer imaging techniques such as Magnetic Resonance Imaging (MRI) and combined Positron Emission Tomography (PET) and Computerized Tomography (CT) has been introduced into clinical practice to better define the skeletal involvement. Currently, the PET/CT with 18 F-fluorodeoxyglucose (FDG) is the diagnostic gold standard to detect active MM bone disease due to the high glycolytic activity of MM cells. However, new tracers are actively under investigation because a portion of MM patients remains negative at the skeletal level by 18 F-FDG. In this review, we will summarize the existing knowledge on the metabolic alterations of MM cells considering their impact on the BM microenvironment cells and particularly in the subsequent formation of osteolytic bone lesions. Based on this, we will discuss the identification of possible new druggable targets and the use of novel metabolic targets for PET imaging in the detection of skeletal lesions, in the staging and treatment response of MM patients.

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Cited by

Sorted by citations

Authors
Raimondi, V., Toscani, D., Marchica, V., Burroughs-Garcia, J., Storti, P., & Giuliani, N.
Affiliations
University of Parma (IT)
Corresponding author
  • Storti, Paola
  • Giuliani, Nicola
ORCID
Venue
Frontiers in Oncology
Publisher
Frontiers Media SA
Published
2022-10-13
Volume
12
Pages
1015402-1015402
ISSN
2234-943X (ISSN-L)
DOI
10.3389/fonc.2022.1015402
PMC
PMC9608343
OpenAlex
W4304889239
Cited by
10
References
10
Citations by year
2026: 4 · 2025: 5 · 2023: 1
FWCI
0.27
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Oncology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Associazione Italiana per la Ricerca sul Cancro (IG2017 ID. 20299)
  • International Myeloma Society (“Paula and Rodeger Riney Foundation Translational Research Grant”)
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
  • Health Sciences › Medicine › Oncology › Bone health and treatments
Keywords
multiple myeloma, myeloma bone disease, bone microenvironment, cancer metabolism, glycolysis, lactic acid production, glucose transporters, glutamine metabolism, osteogenic differentiation, mesenchymal stem cells, bone remodeling, osteolytic lesions, FDG PET/CT, bone marrow plasma cells

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