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Multiple myeloma is one of the most common haematological malignancies, occurring mainly in men over 60 years of age. Despite significant therapeutic progress and a twofold increase in overall survival, multiple myeloma is still an incurable disease. The reason for the relatively poor prognosis for multiple myeloma patients lies in the biology of this tumour, the progressive development of which is closely dependent on the bone marrow microenvironment. The conditions in the bone marrow, in particular, the presence of growth factors for multiple myeloma cells (including interleukin 6, insulin-like growth factor-1, and vascular endothelial growth factor) secreted by different cells, promote their survival and proliferation in the bone marrow niches. Migration and expansion of malignant plasma cells and their mobilisation to/from the peripheral blood, characteristic of myeloma progression, are mainly due to disruption of the stromal cell-derived factor-1/CXCR4 axis caused by numerous molecular extracellular factors. It has been shown that the formation of premetastatic niches in the bone marrow, which are indicative of progression, occurs even before the first metastatic cells, home to the bone marrow, and is affected by cellular and extracellular components of the bone marrow. This close interaction between malignant plasma cells and the bone marrow microenvironment should determine appropriate therapeutic management focused on all elements of this complex biological system for a real improvement in prognosis. This paper reviews the current literature describing the participation of myeloma cells and the bone marrow microenvironment in disease development and progression. Conclusion Novel therapeutic approaches should target not only the malignant plasma cell, but also its interaction with the bone marrow microenvironment to sufficiently prevent disease progression. Despite administration of several immunomodulators and proteasome inhibitors, other therapies are still under active investigation.

The functional significance of the bone marrow microenvironment in multiple myeloma development and progression