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  • Title: [Human leukemic-cell protein-kinases. 1 - Non-granulocytic leukemias (author's transl)].
    Author: Boivin P, Galand C.
    Journal: Nouv Rev Fr Hematol (1978); 1981; 23(5):257-65. PubMed ID: 6276861.
    Abstract:
    The study of human leukemic-cell protein-kinases is justified by two types of arguments: on one hand, abnormal protein-kinases have been found in various malignancies, and on the other the products of virus transforming genes have repeatedly been identified as protein-kinases. Using cytosolic and particulate extracts of normal human lymphocytes we measured protein-kinase activities, then following partial purification by DEAE and phosphocellulose chromatography the isoenzymes of cyclic AMP dependent and independent protein-kinases and casein-kinases were determined in order to establish a profile (12 normal subjects). The same methodology was applied to the lymphocytes of 5 patients with chronic lymphocytic leukemia (CLL) and 3 patients with acute lymphoblastic leukemia (ALL). Compared to normal lymphocytes, the specific activity of cytosolic and particulate extracts from the leukemics was higher for histone and casein-kinases, following elimination of an inhibitory activity present in the crude extracts. Studies of the isoenzymes showed, in some individuals, the presence in both cytosolic and particulate extracts of two important cyclic AMP dependent histone-kinase activities, which were very low or absent in normal lymphocyte extracts. In the particulate extracts we found a constant increase in casein-kinase activities concerning essentially one of the two isoenzymes present. Also, the ratio of the different isoenzymes separated by chromatography was considerably modified with regard to both histone and casein-kinases. These quantitative and qualitative abnormalities were present in some CLL cells and in non-granulocytic acute leukemic cells. They resembled the modification reported during normal lymphocyte stimulation by phytohemagglutinin, and also seemed to reflect the intensity of cellular replication and to some degree the progression of the disease.
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