Abstract
The aim of this pilot study was to determine the plasma levels of monocyte chemotactic protein-1 (MCP-1) and possible associations with angiogenesis and the main clinical features of untreated patients with multiple myeloma (MM). ELISA was used to determine plasma MCP-1 levels in 45 newly diagnosed MM patients and 24 healthy controls. The blood vessels were highlighted by immunohistochemical staining, and computer-assisted image analysis was used for more objective and accurate determination of two parameters of angiogenesis: microvessel density (MVD) and total vascular area (TVA). The plasma levels of MCP-1 were compared to these parameters and the presence of anemia, renal dysfunction, and bone lesions. A significant positive correlation was found between plasma MCP-1 concentrations and TVA (p = 0.02). The MCP-1 levels were significantly higher in MM patients with evident bone lesions (p = 0.01), renal dysfunction (p = 0.02), or anemia (p = 0.04). Therefore, our preliminary results found a positive association between plasma MCP-1 levels, angiogenesis (expressed as TVA), and clinical features in patients with MM. However, additional prospective studies with a respectable number of patients should be performed to authenticate these results and establish MCP-1 as a possible target of active treatment.
Highlights
Multiple myeloma (MM) represents a common hematological neoplasm characterized by monoclonal expansion of plasma cells within the bone marrow, production of monoclonal immunoglobulins, and tissue impairment
monocyte chemotactic protein-1 (MCP-1) was detected in plasma samples from all patients and healthy controls, and no significant differences were found between MM patients and healthy controls
Our results show for the first time a positive correlation between plasma MCP-1 levels and angiogenesis in myeloma patients, as patients with higher plasma MCP1 levels had significantly higher total vascular area (TVA) in Bone marrow biopsies (BMBs), whereas microvessel density (MVD) failed to show a significant association with chemokine concentrations
Summary
Multiple myeloma (MM) represents a common hematological neoplasm characterized by monoclonal expansion of plasma cells within the bone marrow, production of monoclonal immunoglobulins, and tissue impairment. The unpredictable biological behavior of this neoplasm reflects complex interactions between plasma cells and other components of the bone marrow microenvironment. The limited success achieved by targeting only myeloma cells in conventional and/or high-dose chemotherapy highlights the importance of understanding the role of the bone marrow microenvironment and its specific contribution to myelomagenesis. In MM, the microenvironment is composed of clonal plasma cells, extracellular matrix proteins, bone marrow stromal cells, inflammatory cells, and microvessels. Substantial evidence indicates that interactions between these components play a key role in the proliferation and survival of myeloma cells, angiogenic and osteoclastogenic processes, and the development of drug resistance, which all lead to disease progression [2]. The antimyeloma activity of proteasome inhibitors (bortezomib, carfilzomib) and immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide) is based on their capacity to disrupt these pathophysiological processes [3, 4]
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