Is PU.1 a dosage-sensitive regulator of haemopoietic lineage commitment and leukaemogenesis?

Author(s): Dakic, A; Wu, L; Nutt, SL;
Details: Publication Year 2007-03,Volume 28,Issue #3,Page 108-114
Journal Title: TRENDS IN IMMUNOLOGY
Publication Type: Journal Article
Abstract: The transcription factor PU.1 is an essential regulator of haemopoiesis and a suppressor of myelloid leukaemia. PU.1 displays a complex expression pattern characterized by high expression in myelloid cells and low amounts in lymphoid cells. Based on this transcriptional profile, and the analysis of cell lines and mice expressing altered levels of PU.1, a model has been proposed where the concentration of PU.1 determines cell fate, whereas the graded reduction, but not absence, of PU.1 facilitates leukaernogenesis. The recent reports of mouse strains that enable the accurate determination of PU.1 expression and the conditional inactivation of PU.1 in adult haernopoiesis have led us to re-examine our understanding of the complexfunctions of PU.1. Here, we will discussthe data that, we believe, argue against the dosage-sensitive model of PU.1-mediated lineage commitment and leukaemogenesis.
Publisher: ELSEVIER SCI LTD
Keywords: ACUTE MYELOID-LEUKEMIA; TRANSCRIPTION FACTOR PU.1; COLONY-STIMULATING FACTOR; SELF-RENEWAL CAPACITY; BONE-MARROW; STEM-CELLS; C/EBP-ALPHA; LYMPHOID PROGENITORS; FACTOR-RECEPTOR; ETS-DOMAIN
Publisher's Version: https://doi.org/10.1016/j.it.2007.01.006
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2007-03-01 12:00:00