Specific nuclear binding of anti-cdc2 on p34cdc2 positive autonomously grown human leukemia cells induces differentiation.
Intracellular p34cdc2 appears to be responsible for excessive cell growth. Therefore, disturbance of this cell cycle kinase by a specific monoclonal IgG1 anti-cdc2 antibody that specifically recognizes the product of the cdc2 gene, p34, was attempted. By using the surface p34 positive and rapidly proliferating HL-60 human promyelocytic leukemia cell line, transmission electron microscopy (TEM) and other standard techniques, it was found that the antibody, after an initial outer membrane attachment at 4 degrees C and entering the cells by raising the temperature to 37 degrees C, is directed and bound specifically on to the cell's nucleolus. This binding does not only demonstrate the intracellular localization of cdc2, but also appears to disturb its function. It thus induces a class II (HLA-DR) enhancement, increases the phagocytic ability of the cells and causes cellular elongation marked by a non-permanent adherence pattern. The results obtained are IgG independent and indicate that disturbance of constitutive cdc2 expression drives the cells to another level of maturation. The mechanisms behind these actions are still unknown. The results, however, may indicate that the regulatory pathways that govern the functioning of cell cycle stages are actively involved in the processes of cell differentiation. Similar findings have also been released where terminal murine erythro-differentiation may be achieved by manipulation of specific cell cycle kinases. On the contrary, normal already differentiated cdc2 negative human blood-derived monocytes remain insensitive to anti-cdc2 treatment, supporting the view that the presence of this kinase may be one of the reasons leading malignant cells to excessive growth, and that laboratory manipulation and reinfusion of these cells to leukemia patients may be a possible regimen for AML.
Vassiliadis
S
S
Department of Biology, University of Crete, Greece.
Papadogiorgakis
S
S
Athanassakis
I
I
D000911:Antibodies, Monoclonal / Q000378:metabolism; D000937:Antigen-Antibody Reactions; D001692:Biological Transport; D016203:CDC2 Protein Kinase / Q000378:metabolism*; D002451:Cell Compartmentation; D002454:Cell Differentiation; D002466:Cell Nucleolus / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007938:Leukemia / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D006684:HLA-DR Antigens; D016203:CDC2 Protein Kinase