The Bone Marrow Microenvironment in B-Cell Development and Malignancy

• Published in: Cancers Vol. 14; no. 9; p. 2089
• Main Authors: Hughes, Anastasia M, Kuek, Vincent, Kotecha, Rishi S, Cheung, Laurence C
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 22-04-2022; MDPI
• Subjects: Ablation; Acute lymphoblastic leukemia; Adipocytes; Blood vessels; Bone marrow; Cell differentiation; Cytokines; Cytotoxicity; Disease resistance; Endothelial cells; Hematopoietic stem cells; Immune response (humoral); Immune system; Insulin-like growth factors; Ligands; Lymphocytes B; Lymphopoiesis; Malignancy; Mesenchyme; Microenvironments; Osteoclasts; Osteoprogenitor cells; Progenitor cells; Proteins; Review; Roles; Stromal cells; Transgenic animals; B-cell acute lymphoblastic leukemia (B-ALL); B-cell development; leukemia; B-cell niche; bone marrow microenvironment (BMM); bone marrow (BM)
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14092089

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.