BACH2 mediates negative selection and p53-dependent tumor suppression at the pre-B cell receptor checkpoint.

ABSTRACT: The B cell-specific BACH2 transcription factor is required for affinity maturation of mature B cells. Here, we show that Bach2 mediates negative selection at the pre-B cell receptor checkpoint and functions as a critical safeguard against leukemogenesis. Bach2-mediated activation of p53 is required for stringent elimination of pre-B cells that failed to productively rearrange immunoglobulin VH-DJH gene segments, and thus lack pre-B cell receptor expression. Upon productive VH-DJH gene rearrangement, pre-B cell receptor signaling ends negative selection through BCL6-mediated repression of p53. In patients with pre-B acute lymphoblastic leukemia, Bach2-mediated checkpoint control is frequently compromised and low levels of Bach2 expression represent a strong independent predictor of poor cli

ORGANISM(S): Homo sapiens

SUBMITTER: Huimin Geng 

PROVIDER: E-GEOD-44420 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress