microRNAs (miRNAs) are small molecular non-coding RNA with 21-25 nucleotides in a variety of eukaryotic systems, and regulate gene expression at the post-transcriptional level by degrading or translational repressing target messenger RNA (mRNA). Many studies have showed the roles of miRNAs in normal lymphocytopoiesis, giving an interpretative key to the aberrant expression observed in human lymphoid malignancies. The recent advances of understanding the roles of miRNAs in lymphoid malignancies show that miRNAs as tumoral biomarkers can effectively be used for diagnosis, prognosis, and prediction of response to therapy. This review focuses the roles of miRNA in development and differentiation of lymphocytes and the relation of miRNA to lymphoid malignancies.
Cell Differentiation ; Humans ; Lymphocytes ; cytology ; Lymphopoiesis ; genetics ; MicroRNAs ; Neoplasms ; genetics ; pathology ; RNA, Messenger ; genetics

B lymphocytes are produced from hematopoietic stem cells (HSCs) through the highly ordered process of B lymphopoiesis, which is regulated by a complex network of cytokines, chemokines and cell adhesion molecules derived from the hematopoietic niche. Primary osteoblasts function as an osteoblastic niche (OBN) that supports in vitro B lymphopoiesis. However, there are significant limitations to the use of primary osteoblasts, including their relative scarcity and the consistency and efficiency of the limited purification and proliferation of these cells. Thus, development of a stable osteoblast cell line that can function as a biomimetic or artificial OBN is necessary. In this study, we developed a stable osteoblastic cell line, designated OBN4, which functions as an osteoblast-based artificial niche that supports in vitro B lymphopoiesis. We demonstrated that the production of a B220⁺ cell population from Lineage⁻ (Lin⁻) Sca-1⁺ c-Kit⁺ hematopoietic stem and progenitor cells (HSPCs) was increased ~1.7-fold by OBN4 cells relative to production by primary osteoblasts and OP9 cells in coculture experiments. Consistently, OBN4 cells exhibited the highest production of B220⁺ IgM⁺ cell populations (6.7±0.6–13.6±0.6%) in an IL-7- and stromal cell-derived factor 1-dependent manner, with higher production than primary osteoblasts (3.7±0.5–6.4±0.6%) and OP9 cells (1.8±0.6–3.9±0.5%). In addition, the production of B220⁺ IgM⁺ IgD⁺ cell populations was significantly enhanced by OBN4 cells (15.4±1.1–18.9±3.2%) relative to production by primary osteoblasts (9.5±0.6–14.6±1.6%) and OP9 cells (9.1±0.5–10.3±1.8%). We conclude that OBN4 cells support in vitro B lymphopoiesis of Lin⁻ Sca-1⁺ c-Kit⁺ HSPCs more efficiently than primary osteoblasts or OP9 stromal cells.
B-Lymphocytes ; Biomimetics ; Cell Adhesion Molecules ; Cell Line ; Chemokines ; Coculture Techniques ; Cytokines ; Hematopoietic Stem Cells ; In Vitro Techniques* ; Lymphopoiesis* ; Osteoblasts ; Stem Cells ; Stromal Cells