Homing behaviour of the malignant cell clone in multiple myeloma

Multiple myeloma (MM) represents a B cell malignancy characterised by the presence of a monoclonal population of end-stage B cells in the bone marrow. Although fully matured bone marrow plasma cells are the predominant cell type in MM, there is much evidence that also more immature B cells are included in the malignant cell clone which are considered to be the myeloma precursor cells. The fact that these cells are detectable in the blood circulation and that their number increases with disease progression, makes it very likely that they represent the component of the tumour clone that mediates disease dissemination. This implies that these cells must have the potential to extravasate and home to the bone marrow environment. Like the migration mechanisms used by normal leukocytes and/or metastatic tumour cells of non-haematopoietic origin, it can be assumed that this bone marrow homing process is mediated by adhesive interactions and chemotactic signals provided by the microenvironment of the tumour. Once in the bone marrow compartment, myeloma cells will receive the appropriate signals to grow and survive. This aspect of tumour-homing is found to be the result of a functional interplay between the myeloma cells and the surrounding microenvironment, involving the action of several cytokines and adhesion molecules. In the end phase of the disease, myeloma cells can lose their stroma-dependency resulting in extramedullary tumour growth. We review normal B cell homing and discuss molecular mechanisms that determine the homing behaviour of the malignant cell clone in MM.