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Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
Published on: September 1, 2019
RUNX expression and function in human B cells
Hannah J Whiteman1, Paul J Farrell
1Department of Virology, Imperial College Faculty of Medicine, St. Mary's Campus, Norfolk Place, London W2 1PG, UK.
Abstract:
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.
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