Determination of levels and isozymic patterns of
protein kinase activities was performed upon extracts from two human
leukemia cell lines (K562 and HL-60) and blast cells from five untreated patients with
acute myeloblastic leukemia and compared to activities from normal human peripheral blood granulocytes and bone marrow samples enriched for proliferative myeloid cells. The leukemic cells studied were found to have higher specific activities of cytosol cyclic
adenosine 3':5'-monophosphate (cAMP)-independent
casein kinase and lower activation by cAMP of their cytosol
histone kinase compared to the normal myeloid cells studied.
Diethylaminoethyl-cellulose chromatography revealed correspondingly higher amounts of cAMP-independent
protein kinase isoenzymes (two
casein kinase and one
histone kinase peaks) in the leukemic cells, as well as altered ratios of the two cAMP-dependent
isozymes.
Casein phosphorylating activities extracted from the nuclei of the leukemic cell lines were also high compared to normal myeloid cells. Further purification and estimation of molecular weights of the
isoenzymes present in
leukemia were accomplished by gel filtration, using
Sephacryl S-200. Resolution of the
acute myeloblastic leukemia cell line nuclear
casein kinase activity into two peaks was also thereby accomplished. The nuclear peaks eluted earlier than the corresponding cytoplasmic peaks; thus, the nuclear
isoenzymes may not be identical to those from the cytoplasm. The increased
protein kinase activity noted in such cells may be an important biochemical concomitant of transformation.