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[Cancer Research 41, 2182-2188, June 1, 1981]
© 1981 American Association for Cancer Research

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Cyclic Adenosine 3':5'-Monophosphate-dependent and -independent Protein Kinase in Acute Myeloblastic Leukemia1

Laurence Elias2, Albert P. Li3 and Jonathan Longmire

Department of Medicine and Cancer Research and Treatment Center, University of New Mexico School of Medicine, Albuquerque, New Mexico 87131

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.

1 This work was supported in part by a grant from the National Leukemia Association, Inc., and by USPHS Core Support Grant CA21074 to the Cancer Research and Treatment Center. Presented in part at the June 1980 annual meeting of the American Society of Biological Chemists, New Orleans, La.

2 To whom requests for reprints should be addressed.

3 Present address: Lovelace Foundation, Inhalation Toxicology Research Institute, Kirtland Air Force Base, Albuquerque, N. M. 87116.

Received 7/21/80. Accepted 2/23/81.




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Copyright © 1981 by the American Association for Cancer Research.