Abstract
Multiple myeloma (MM) is one of the most common forms of hematologic malignancy resulting from cancerous proliferation of mature malignant plasma cells (MPCs). But despite the real improvement in therapeutics in the past years, it remains largely incurable. MM is the most frequent cancer to involve bone due to the stimulation of osteoclast (OCL) differentiation and activity. OCLs have a unique capacity to resorb bone. However, recent studies reveal that they are not restrained to this sole function. They participate in the control of angiogenesis, medullary niches, and immune responses, including in MM. Therefore, therapeutic approaches targeting OCLs probably affect not only bone resorption but also many other functions, and OCLs should not be considered anymore only as targets to improve the bone phenotype but also to modulate bone microenvironment. In this review, we explore these novel contributions of OCLs to MM which reveal their strong implication in the MM physiopathology. We also underline the therapeutic interest of targeting OCLs not only to overcome bone lesions, but also to improve bone microenvironment and anti-tumoral immune responses.
Highlights
Representing 13% of hematologic and 1% of all the cancers [1], multiple myeloma (MM) is the most common form of hematologic malignancy after non-Hodgkin lymphoma and the most frequent cancer to involve bone [2]
Genetic analysis has demonstrated that the pre-malignant plasma cells (MPCs) share some of the mutations associated with MM and that the disease progresses through multiple genetic waves of MM cell clones [3, 4]
In 2004, Rivollier et al reported for the first time the in vitro differentiation of human dendritic cells (DCs) generated from circulating blood MNs toward mature OCLs under macrophage-colony stimulating factor (M-CSF) and RANKL stimulation and in the presence of synovial fluid from arthritic patients [59]
Summary
Microenvironment and Immune Suppression in Multiple Myeloma. Multiple myeloma (MM) is one of the most common forms of hematologic malignancy resulting from cancerous proliferation of mature malignant plasma cells (MPCs). Recent studies reveal that they are not restrained to this sole function. They participate in the control of angiogenesis, medullary niches, and immune responses, including in MM. Therapeutic approaches targeting OCLs probably affect bone resorption and many other functions, and OCLs should not be considered anymore only as targets to improve the bone phenotype and to modulate bone microenvironment. We underline the therapeutic interest of targeting OCLs to overcome bone lesions, and to improve bone microenvironment and anti-tumoral immune responses
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