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.