Losing B cell identity.

The transcription factor Pax5 is essential for the initial commitment of hematopoietic progenitors to the B cell lineage. Recently, our understanding of the lineage commitment process has been extended with the finding that Pax5 is also continuously required throughout B cell development to reinforce commitment, as inactivation of Pax5 in mature B cells results in their de-differentiation to a progenitor stage that is capable of multi-lineage potential. The reliance of B cell identity on a single gene is not without its problems as the loss of Pax5 results in B cell malignancies in mouse models and mutation in human PAX5 is the most-common genetic lesion in acute lymphoblastic leukemia.