Regulation of DNA-dependent protein kinase activity in leukemic cells.
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.
Muller
C
C
Service d'hématologie, CHU Purpan, Toulouse, France.
Salles
B
B
D000368:Aged; D002457:Cell Extracts; D002467:Cell Nucleus / Q000201:enzymology; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000201:enzymology*; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D009353:Zinostatin / Q000494:pharmacology
D002457:Cell Extracts; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D009353:Zinostatin; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D017346:Protein Serine-Threonine Kinases