okadaic-acid and Leukemia--Lymphocytic--Chronic--B-Cell

okadaic-acid has been researched along with Leukemia--Lymphocytic--Chronic--B-Cell* in 1 studies

Other Studies

1 other study(ies) available for okadaic-acid and Leukemia--Lymphocytic--Chronic--B-Cell

Article	Year
Human chronic lymphocytic leukemia B cells can escape DNA damage-induced apoptosis through the nonhomologous end-joining DNA repair pathway. Blood, 2005, Jun-15, Volume: 105, Issue:12 Nonhomologous end-joining (NHEJ) DNA factors maintain genomic stability through their DNA double-strand break (DSB) repair and telomere-associated activities. Unrepaired or misrepaired DSBs can lead to apoptotic death or chromosomal damage. The B cells of some B-chronic lymphocytic leukemia (B-CLL) patients are resistant to radiation-induced apoptosis in vitro. We show here that the novel DNA-dependent protein kinase (DNA-PK) inhibitor, NU7026 (2-(morpholin-4-yl)-benzo[h]chomen-4-one), and the phosphatidylinositol 3 (PI-3) kinase inhibitor, wortmannin, restored sensitivity to DNA damage-induced apoptosis of otherwise resistant cells. These resistant malignant B cells also escaped DSB-induced apoptosis following exposure to etoposide or neocarzinostatin. We found that at 15 minutes after irradiation, the levels of NHEJ (as measured by an in vitro DSB end-ligation assay) and DNA-PK catalytic subunit (DNA-PKcs) activity were, respectively, 2-fold and 4-fold higher in radio-resistant than in radio-sensitive B-CLL cells or Epstein-Barr virus (EBV)-transformed B cells. Ku70/Ku80 heterodimer DNA end-binding activity was also 2- to 3-fold higher in the resistant B-CLL cell subset compared with the sensitive B-CLL cell subset. Our results provide the first evidence that overactivating the NHEJ DNA repair pathway impairs DNA damage-induced apoptosis in malignant B cells and that this may contribute to their resistance to current chemotherapy. Topics: Androstadienes; Antibiotics, Antineoplastic; Antigens, Nuclear; Antineoplastic Agents, Phytogenic; Apoptosis; B-Lymphocytes; Blotting, Western; Cell Line, Transformed; Cell Line, Tumor; Cell-Free System; Chromones; Dimerization; DNA; DNA Damage; DNA Repair; DNA-Binding Proteins; Dose-Response Relationship, Drug; Enzyme Inhibitors; Etoposide; Gamma Rays; Humans; Ku Autoantigen; Leukemia, Lymphocytic, Chronic, B-Cell; Morpholines; Okadaic Acid; Phosphatidylinositol 3-Kinases; Protein Binding; Telomere; Time Factors; Wortmannin; Zinostatin	2005

Article

Year

Human chronic lymphocytic leukemia B cells can escape DNA damage-induced apoptosis through the nonhomologous end-joining DNA repair pathway.

Blood, 2005, Jun-15, Volume: 105, Issue:12

Nonhomologous end-joining (NHEJ) DNA factors maintain genomic stability through their DNA double-strand break (DSB) repair and telomere-associated activities. Unrepaired or misrepaired DSBs can lead to apoptotic death or chromosomal damage. The B cells of some B-chronic lymphocytic leukemia (B-CLL) patients are resistant to radiation-induced apoptosis in vitro. We show here that the novel DNA-dependent protein kinase (DNA-PK) inhibitor, NU7026 (2-(morpholin-4-yl)-benzo[h]chomen-4-one), and the phosphatidylinositol 3 (PI-3) kinase inhibitor, wortmannin, restored sensitivity to DNA damage-induced apoptosis of otherwise resistant cells. These resistant malignant B cells also escaped DSB-induced apoptosis following exposure to etoposide or neocarzinostatin. We found that at 15 minutes after irradiation, the levels of NHEJ (as measured by an in vitro DSB end-ligation assay) and DNA-PK catalytic subunit (DNA-PKcs) activity were, respectively, 2-fold and 4-fold higher in radio-resistant than in radio-sensitive B-CLL cells or Epstein-Barr virus (EBV)-transformed B cells. Ku70/Ku80 heterodimer DNA end-binding activity was also 2- to 3-fold higher in the resistant B-CLL cell subset compared with the sensitive B-CLL cell subset. Our results provide the first evidence that overactivating the NHEJ DNA repair pathway impairs DNA damage-induced apoptosis in malignant B cells and that this may contribute to their resistance to current chemotherapy.

Topics: Androstadienes; Antibiotics, Antineoplastic; Antigens, Nuclear; Antineoplastic Agents, Phytogenic; Apoptosis; B-Lymphocytes; Blotting, Western; Cell Line, Transformed; Cell Line, Tumor; Cell-Free System; Chromones; Dimerization; DNA; DNA Damage; DNA Repair; DNA-Binding Proteins; Dose-Response Relationship, Drug; Enzyme Inhibitors; Etoposide; Gamma Rays; Humans; Ku Autoantigen; Leukemia, Lymphocytic, Chronic, B-Cell; Morpholines; Okadaic Acid; Phosphatidylinositol 3-Kinases; Protein Binding; Telomere; Time Factors; Wortmannin; Zinostatin

2005