Reduced expression of aphidicolin-induced common fragile sites in peripheral lymphocyte chromosomes of patients with B-cell chronic lymphocytic leukemia.
The occurrence and frequency of aphidicolin-induced common chromosomal fragile sites were examined in 12 B-cell chronic lymphocytic leukemia (B-CLL) patients (ten males and two females) and three normal individuals. The mononuclear cells separated by Ficoll-Hypaque gradient were cultured in vitro for 96 hours stimulated by pokeweed mitogen (PWM) in combination with T-leukemia cell conditioned medium or 10% B-cell growth factor. For the final 24 hours the cells were treated with aphidicolin (0.07 microgram/ml). Results indicate that there was a significant reduction in the overall mean frequency of common fragile sites in CLL patients with a wide individual variation. Fragile sites were found to be localized either on a single chromatid or both chromatids, but rarely involved homologous chromosomes. No definite relationship between the frequency of fragile sites and the staging of CLL disease was observed. A significant reduction and variability in the frequency of fragile sites suggest the heterogenous nature of B-CLL and probably a different mechanism of induction of fragile sites in CLL cells compared to controls.
Nayak
B N
BN
Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada.
Ray
M
M
D016590:Aphidicolin; D002478:Cells, Cultured; D043283:Chromosome Fragile Sites; D002873:Chromosome Fragility; D004257:DNA Polymerase II / Q000037:antagonists & inhibitors; D004224:Diterpenes / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007621:Karyotyping; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008214:Lymphocytes / Q000187:drug effects / Q000648:ultrastructure; D008297:Male
D004224:Diterpenes; D016590:Aphidicolin; D004257:DNA Polymerase II