p53 expression in K562 cells is associated with caspase‐mediated cleavage of c‐ABL and BCR–ABL protein kinases

Abstract

Summary. The chimaeric BCR‐ABL oncoprotein is the molecular hallmark of chronic myeloid leukaemia (CML). Expression of Bcr‐Abl has been associated with arrested differentiation as well as resistance to apoptosis. The downstream pathway involved in apoptosis resistance has been extensively studied, whereas the role of Bcr‐Abl in cell differentiation is largely unclear. A recent report has shown that Bcr‐Abl expression alone is sufficient to increase the number of multipotent and myeloid lineage‐committed progenitors in a dose‐dependent manner while suppressing the development of committed erythroid progenitors. In accordance with this model, downregulation of c‐Abl and Bcr‐Abl has been observed during differentiation in different systems, although the mechanism is still largely unknown. To investigate the relationship between erythroid differentiation and c‐Abl and Bcr‐Abl levels, we induced differentiation in K562 cells using a temperature‐inducible p53 mutant (p53Val1335). It was found that p53‐induced erythroid differentiation in K562 cells required caspase activity. During this process, caspase‐dependent cleavage of c‐Abl and Bcr‐Abl tyrosine kinases was observed, suggesting a new mechanism for the downregulation of the kinases during erythroid differentiation.