Myeloblastin is an Myb target gene: mechanisms of regulation in myeloid leukemia cells growth-arrested by retinoic acid

A pivotal role has been assigned to Myb in the control of myeloid cell grow th. Although Myb is a target of retinoic acid, little is known about the me chanisms by which it may contribute to induced growth arrest in leukemia ce lls. Indeed, few Myb target genes are known to be linked to proliferation. Myeloblastin is involved in the control of proliferation in myeloid leukemi a cells. It is expressed early during hematopoiesis and is a granulocyte co lony-stimulating factor-responsive gene. Myeloblastin can confer factor-ind ependent growth to hematopoietic cells, an early step in leukemia transform ation. The myeloblastin promoter contains PU.1, C/EBP, and Myb binding site s, each of which are critical for constitutive expression in myeloid cells. Inhibition of myeloblastin expression in leukemia cells growth-arrested by retinoic acid is demonstrated to depend on Myb downregulation. Myb is show n to induce myeloblastin expression and abolish its down-regulation by reti noic acid. Altogether, the data offer a clue as to how a myeloid-specific t ranscriptional machinery can be accessible to regulation by retinoic acid a nd point to myeloblastin as a novel target of Myb. This link between Myb an d myeloblastin suggests a previously nonidentified Myb pathway through whic h growth arrest is induced by retinoic acid in myeloid leukemia cells. (Blo od. 2001;97:2449-2456) (C) 2001 by The American Society of Hematology.