Suppression of erythroid but not megakaryocytic differentiation of human K562 erythroleukemic cells by Notch-1

The Notch signal transduction pathway is a highly conserved regulatory syst em that controls multiple developmental processes. We have established an e rythroleukemia cell model to study how Notch regulates cell fate and erythr oleukemic cell differentiation. K562 and HEL cells expressed the Notch-1 re ceptor and the Notch ligand Jagged-1. The stable expression of the constitu tively active intracellular domain of Notch-1 (NIC-1) in K562 cells inhibit ed erythroid without affecting megakaryocytic maturation. Expression of ant isense Notch-1 induced spontaneous erythroid maturation. Suppression of ery throid maturation by NIC-1 did not result from down-regulation of GATA-1 an d TAL-1, transcription factors necessary for erythroid differentiation. Mic roarray gene expression analysis identified genes activated during erythroi d maturation, and NIC-1 disrupted the maturation-dependent changes in the e xpression of these genes. These results show that NIC-1 alters the pattern of gene expression in K562 cells leading to a block in erythroid maturation and therefore suggest that Notch signaling may control the developmental p otential of normal and malignant erythroid progenitor cells.