The cyclin-dependent kinase inhibitors p18INK4c and p19INK4d are highly expressed in CD34+ progenitor and acute myeloid leukaemic cells but not in normal differentiated myeloid cells.
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 p18INK4c and p19INK4d in leukaemic and CD34+ progenitor cells than in granulocytes and monocytes. A different pattern was seen for p27Kip1 and p57Kip2 expression being low in leukaemic cells but high in normal immature and differentiated cells. No marked differences were found in p15INK4b and p21Cip1 mRNA expression between leukaemic and CD34+ progenitor or mature myeloid cells. Our findings therefore indicate that high expression of p18INK4c and p19INK4d in haemopoietic progenitor and leukaemic blast cells may contribute to the premature differentiation block seen in AML.
Tschan
M P
MP
Department of Clinical Research, University of Berne, Switzerland.
Peters
U R
UR
Cajot
J F
JF
Betticher
D C
DC
Fey
M F
MF
Tobler
A
A
D000208:Acute Disease; D018952:Antigens, CD34; D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050764:Cyclin-Dependent Kinase Inhibitor p19; D004791:Enzyme Inhibitors / Q000378:metabolism*; D018922:HL-60 Cells; D006412:Hematopoietic Stem Cells / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007951:Leukemia, Myeloid / Q000201:enzymology* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
D018952:Antigens, CD34; C493971:CDKN2C protein, human; C493974:CDKN2D protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050764:Cyclin-Dependent Kinase Inhibitor p19; D004791:Enzyme Inhibitors; D025521:Tumor Suppressor Proteins