The Bone Marrow Microenvironment in B-Cell Development and Malignancy

SIMPLE SUMMARY: B cells are an essential component of the immune system and develop in the bone marrow microenvironment. B-cell development is tightly regulated by the stromal cells, fat cells and bone cells in this microenvironment. However, when B-cell malignancies arise, leukemic cells can alter normal microenvironment functioning to aid their growth, survival and resistance to cytotoxic therapies. This review summarizes the role of the bone marrow microenvironment in regulating healthy B-cell development and B-cell acute lymphoblastic leukemia (B-ALL). Understanding of how the microenvironment contributes to B-ALL pathogenesis and treatment failure will allow us to devise microenvironment-targeted therapies for B-ALL in the future. ABSTRACT: B lymphopoiesis is characterized by progressive loss of multipotent potential in hematopoietic stem cells, followed by commitment to differentiate into B cells, which mediate the humoral response of the adaptive immune system. This process is tightly regulated by spatially distinct bone marrow niches where cells, including mesenchymal stem and progenitor cells, endothelial cells, osteoblasts, osteoclasts, and adipocytes, interact with B-cell progenitors to direct their proliferation and differentiation. Recently, the B-cell niche has been implicated in initiating and facilitating B-cell precursor acute lymphoblastic leukemia. Leukemic cells are also capable of remodeling the B-cell niche to promote their growth and survival and evade treatment. Here, we discuss the major cellular components of bone marrow niches for B lymphopoiesis and the role of the malignant B-cell niche in disease development, treatment resistance and relapse. Further understanding of the crosstalk between leukemic cells and bone marrow niche cells will enable development of additional therapeutic strategies that target the niches in order to hinder leukemia progression.