RUNX expression and function in human B cells.
RUNX1 and RUNX3 are expressed at many stages of B-cell differentiation, suggesting that they play a role in the development and functions of this lineage. Transgenic mice lacking expression of RUNX1 or the RUNX protein-binding partner, CBFbeta, have defective B-cell development, with differentiation blocked at an early stage. Specific knockout of RUNX1 in adult hematopoietic cells also caused a decrease in the number of mature B cells, supporting a role for RUNX1 in both developmental and adult hematopoiesis. Furthermore, RUNX proteins have been shown to regulate several B-cell-specific genes and play an important role in TGF-beta-induced immunoglobulin class switching to IgA. The importance of RUNX1 in B-cell development is additionally demonstrated by its dysregulation in the t(12;21) translocation, which is the most frequent translocation found in acute lymphocytic leukemia. Epstein Barr virus immortalized human B lymphoblastoid cell lines express RUNX3, and cross-regulation of RUNX1 by RUNX3 occurs in these cells. Knockdown of RUNX3 in these cells induces RUNX1 expression and inhibits cell proliferation, directly showing that RUNX proteins can regulate B-cell growth.
Department of Virology, Imperial College Faculty of Medicine, St. Mary's Campus, Norfolk Place, London W2 1PG, UK.
Hannah J
HJ
Whiteman
Paul J
PJ
Farrell
D001402:B-Lymphocytes / Q000276:immunology*; D050657:Core Binding Factor alpha Subunits / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D015448:Leukemia, B-Cell / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics*; D015398:Signal Transduction; D016211:Transforming Growth Factor alpha / Q000378:metabolism
D050657:Core Binding Factor alpha Subunits; D016211:Transforming Growth Factor alpha