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Review
. 2022 Apr 26;11(2):IJH39.
doi: 10.2217/ijh-2021-0017. eCollection 2022 Apr.

Adhesion molecules in multiple myeloma oncogenesis and targeted therapy

Maroun Bou Zerdan  1 , Lewis Nasr  2 , Joseph Kassab  2 , Ludovic Saba  2 , Myriam Ghossein  3 , Marita Yaghi  1 , Barbara Dominguez  1 , Chakra P Chaulagain  1
Affiliations
Review

Adhesion molecules in multiple myeloma oncogenesis and targeted therapy

Maroun Bou Zerdan et al. Int J Hematol Oncol. .

Abstract

Every day we march closer to finding the cure for multiple myeloma. The myeloma cells inflict their damage through specialized cellular meshwork and cytokines system. Implicit in these interactions are cellular adhesion molecules and their regulators which include but are not limited to integrins and syndecan-1/CD138, immunoglobulin superfamily cell adhesion molecules, such as CD44, cadherins such as N-cadherin, and selectins, such as E-selectin. Several adhesion molecules are respectively involved in myelomagenesis such as in the transition from the precursor disorder monoclonal gammopathy of undetermined significance to indolent asymptomatic multiple myeloma (smoldering myeloma) then to active multiple myeloma or primary plasma cell leukemia, and in the pathological manifestations of multiple myeloma.

Keywords: bone marrow microenvironment; cellular adhesion molecules; drug resistance; monoclonal antibody; multiple myeloma; targeted therapies.

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Conflict of interest statement

Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Figures

Figure 1.
Figure 1.. The process of leukocyte extravasation and the role of cell adhesion molecules.
Figure 2.
Figure 2.. Overview of the bone marrow's immune microenvironment.
The bone marrow microenvironment is divided into endosteal, and vascular niches set within a stroma of differentiated accessory or ‘stromal’ cells, such as fibroblasts, osteoclasts, osteoblasts, adipocytes, endothelial cells, macrophages and mast cells as well as ECM proteins. As for the term ‘immune microenvironment’, it refers to a functional compartment of differentiated immune cells located throughout the marrow stroma. DC: Dendritic cell; ECM: Extracellular matrix; MDSC: Myeloid-derived suppressor cell; PC: Plasma cell.
Figure 3.
Figure 3.. Anti-CD38 monoclonal antibodies mechanisms of action.
Top left: mAbs bind CD38. The Fc fragment is bound by C1q, initiating the complement cascade, and resulting in a membrane attack complex, leading to cell lysis and death. Top right: mAbs bind CD38. The Fc fragment is then bound by an FcR-bearing effector cell, such as a natural killer cell, leading to activation of cytotoxic processes. Bottom left: mAbs bind CD38, and its Fc fragment is then bound by an FcR-bearing macrophage, inducing phagocytosis. Bottom right: FcR-mediated crosslinking of mAbs induces direct cellular apoptosis. ADCC: Antibody-dependent cell-mediated cytotoxicity; ADCP: Antibody-dependent cellular phagocytosis; CDC: Complement-dependent cytotoxicity; MAC: Membrane attack complex; MM: Multiple myeloma.
See this image and copyright information in PMC

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