Anti-Apoptotic Role of Protein-Tyrosine Kinases During Granulocytic Differentiation of HL-60 Cells

Summary

The human promyelocytic leukemia cell line HL-60 can be induced to differentiate towards neutrophils and subsequently die via apoptosis in vitro In this paper, we investigated the roles of protein tyrosine kinases (PTKs) in retinoic acid (RA)-induced granulocytic differentiation of HL-60 cells. Accompanying the RA-induced differentiation, Lyn and Fgr PTKs were phosphorylated on their tyrosine residues and their activities were induced. The degree of both activities and tyrosinephosphorylation of these PTKs was reduced to be minimal at day 5 when the HL-60 cells start to be dead by apoptosis. The inhibitors of PTKs, herbimycin A and genistine, were demonstrated to cause premature cell death of HL-60 cells in the presence of RA. The death was the consequence of an apoptotic process. The RA-treated HL-60 cells, when incubated with specific c-lyn or c-fgr antisense oligodeoxy-nucleotide, also underwent premature death. These data implicate that Lyn and Fgr PTKs prevent programmed cell death to promote granulocytic differentiation of HL-60 cells.