The role of protein kinase C epsilon in the pathogenesis and treatment resistance of Acute Myeloid Leukaemia

Acute myeloid leukaemia (AML) is a heterogeneous group of haematological malignancies, characterised by the accumulation of abnormally differentiated blast cells in the bone marrow. For most patients, prognosis remains poor due to the prevalence of relapse. Protein kinase C epsilon (PKCε) is a pleiotropic regulator of cell signalling which has demonstrated oncogenic properties and in solid cancers, high PKCε expression is associated with poor outcomes. The aim of this study was to determine the clinical significance and functionality of PKCε in AML. Existing protein expression data showed that PKCε was significantly upregulated in 37% (26/70) of AML patient samples and was associated with reduced CR (p<0.05). To support this, I analysed an independent mRNA dataset where high PKCε expression correlated with significantly reduced overall (p<0.05) and disease-free survival (p<0.05). Together these data suggest that high PKCε expression is associated with poor outcomes in AML. Functionality was investigated by modulating PKCε in normal human haematopoietic cells where PKCε overexpression promoted monocyte differentiation. This finding is inconsistent with a role in leukaemogenesis. Instead, it was hypothesized that PKCε may promote chemoresistance. In two AML cell lines, PKCε overexpression conferred daunorubicin (DNR) resistance (p