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Regulation of DNA-dependent protein kinase activity in leukemic cells

Oncogene volume 15, pages 2343–2348 (1997)Cite this article

Abstract

The DNA-dependent protein kinase (DNA-PK) complex is composed of a catalytic (DNA-PKcs), and a regulatory subunit (Ku70/Ku86 heterodimer). The expression and function of DNA-PK subunits was investigated in purified blood lymphocytes obtained from patients with chronic lymphocytic leukemia (CLL) either refractory to chemotherapy or untreated. Variations in DNA-PK activity were found amongst CLL samples by comparison to human cell lines. It was noticeable that the low DNA-PK activity was associated with samples from untreated patients that exhibited a sensitivity phenotype, determined in vitro, to the radiomimetic agent neocarcinostatin by comparison to samples from refractory patients. The regulation in DNA-PK activity was associated with Ku heterodimer expression while DNA-PKcs was unaffected. Moreover, the presence of an altered form of the Ku86 subunit was identified in samples with low DNA-PK activity. These results suggest a regulation process of the DNA-PK activity in fresh human cells.

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Authors and Affiliations

  1. Service d'hématologie, CHU Purpan, Toulouse, 31300, France

    Catherine Muller

  2. Institut de Pharmacologie et de Biologie Structurale, CNRS UPR 9062, 205 route de Narbonne, Toulouse Cedex, 31077, France

    Catherine Muller & Bernard Salles

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  1. Catherine Muller
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  2. Bernard Salles
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Muller, C., Salles, B. Regulation of DNA-dependent protein kinase activity in leukemic cells. Oncogene 15, 2343–2348 (1997). https://doi.org/10.1038/sj.onc.1201402

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  • DOI: https://doi.org/10.1038/sj.onc.1201402

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