Pathophysiology of Protein Kinase C Isozymes in Chronic Lymphocytic Leukaemia

Abstract

This chapter will review the roles of protein kinase C (PKC) isozymes in chronic lymphocytic leukaemia (CLL) cells. PKC family proteins are central to many signalling pathways within cells, and some have been implicated in the oncogenesis of numerous cancers (Benimetskaya, et al., 2001;Keenan, et al., 1999;O'Brian, 1998). In CLL, inhibitors of PKC signalling have been shown to have cytotoxic effects on the malignant cells, and the ,  and  isoforms of PKC have been shown to have pathophysiological roles (Holler, et al., 2009;Nakagawa, et al., 2006;Ringshausen, et al., 2002). The aim of this chapter is to discuss whether PKC can be considered a drug target in the treatment of this disease. We will examine how inhibitors of PKCs have been used in past preclinical studies of CLL, and will discuss the roles of various PKC isozymes (namely PKCII, PKC, PKC and PKC) in the pathology of CLL. This chapter will end with the proposal that inhibition of PKC may be useful in combination therapy through a potential role in regulating Mcl-1 expression.