The cyclin-dependent kinase inhibitors p18(INK4c) and p19(INK4d) are highly expressed in CD34(+) progenitor and acute myeloid leukaemic cells but notin normal differentiated myeloid cells

Cyclin-dependent kinase inhibitors (CKI) are important for the differentiat ion of cells in various tissues. In acute myeloid leukaemia (AML) the cells accumulate at particular stages of myeloid maturation. We therefore analys ed the expression pattern of different CKIs in fresh samples of AML patient s and compared it with that in CD34(+) progenitor and normal differentiated myeloid cells. Competitive RT-PCR and Western analysis revealed a signific antly 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(Lip1) and p57(Kip2) expression being low in leukaemic cel ls but high in normal immature and differentiated cells. No marked differen ces were found in p15(INK4b) and p21(Cip1) mRNA expression between leukaemi c and CD34(+) progenitor or mature myeloid cells. Our findings therefore in dicate that high expression of p18(INK4c) and p19(INK4d) in haemopoietic pr ogenitor and leukaemic blast cells may contribute to the premature differen tiation block seen in AML.