The Hemopoietic Stem Cell Niche Versus the Microenvironment of the Multiple Myeloma-Tumor Initiating Cell

Multiple myeloma cells are reminiscent of hemopoietic stem cells in their strict dependence upon the bone marrow microenvironment. However, from all other points of view, multiple myeloma cells differ markedly from stem cells. The cells possess a mature phenotype and secrete antibodies, and have thus made the whole journey to maturity, while maintaining a tumor phenotype. Not much credence was given to the possibility that the bulk of plasma-like multiple myeloma tumor cells is generated from tumor-initiating cells. Although interleukin-6 is a major contributor to the formation of the tumor’s microenvironment in multiple myeloma, it is not a major factor within hemopoietic stem cell niches. The bone marrow niche for myeloma cells includes the activity of inflammatory cytokines released through osteoclastogenesis. These permit maintenance of myeloma cells within the bone marrow. In contrast, osteoclastogenesis constitutes a signal that drives hemopoietic stem cells away from their bone marrow niches. The properties of the bone marrow microenvironment, which supports myeloma cell maintenance and proliferation, is therefore markedly different from the characteristics of the hemopoietic stem cell niche. Thus, multiple myeloma presents an example of a hemopoietic tumor microenvironment that does not resemble the corresponding stem cell renewal niche.