The cyclin-dependent kinase inhibitors p18(INK4c) and p19(INK4d) are highly expressed in CD34+ progenitor and acute myeloid leukaemic cells but not in normal differentiated myeloid cells

Abstract

Cyclin-dependent kinase inhibitors (CKIs) are important for the differentiation of cells in various tissues. In acute myeloid leukaemia (AML) the cells accumulate at particular stages of myeloid maturation. We therefore analysed the expression pattern of different CKIs in fresh samples of AML patients and compared it with that in CD34+ progenitor and normal differentiated myeloid cells. Competitive RT-PCR and Western analysis revealed a significantly higher expression of p18(INK4c) and p19(INK4d) in leukaemic and CD34+ progenitor cells than in granulocytes and monocytes. A different pattern was seen for p27(Kip1) and p57(Kip2) expression being low in leukaemic cells but high in normal immature and differentiated cells. No marked differences were found in p15(INK4b) and p21(Cip1) mRNA expression between leukaemic and CD34+ progenitor or mature myeloid cells. Our findings therefore indicate that high expression of p18(INK4c) and p19(INK4d) in haemopoietic progenitor and leukaemic blast cells may contribute to the premature differentiation block seen in AML.