P53-INDEPENDENT INDUCTION OF WAF1 C1P1 IN HUMAN LEUKEMIA-CELLS IS CORRELATED WITH GROWTH ARREST ACCOMPANYING MONOCYTE/MACROPHAGE DIFFERENTIATION/

The p53 tumor suppressor gene plays a role in controlling a G(1) phase checkpoint. The WAF1/CIP1 gene with encodes p21(WAF1/CIP1) protein, a n inhibitor of cyclin-dependent kinases, is a downstream mediator of p 53 function, We examined expression of the WAF1/CIP1 gene and its rela tionship to growth arrest and differentiation in p53-null human leukem ic cell Lines. We show that p53-independent induction of WAF1/CIP1 occ urs in human leukemia cells treated with 12-O-tetradecanoylphorbol-13- acetate, okadaic acid, or IFN-gamma but not with retinoic acid, vitami n D-3, or DMSO. Furthermore, WAF1/CIP1 induction correlates with growt h arrest associated with monocyte-macrophage differentiation. The pres ent studies support the idea that WAF1/CIP1 gene expression can be reg ulated through multiple mechanisms, suggesting that strategies may be designed to restore the G(1) checkpoint controls in p53-null cells by targeting these p53-independent mechanisms of WAF1/CIP1 induction.