bmn-673 and Leukemia--Lymphocytic--Chronic--B-Cell

bmn-673 has been researched along with Leukemia--Lymphocytic--Chronic--B-Cell* in 2 studies

Other Studies

2 other study(ies) available for bmn-673 and Leukemia--Lymphocytic--Chronic--B-Cell

Article	Year
CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions. Nature, 2018, Volume: 559, Issue:7713 The observation that BRCA1- and BRCA2-deficient cells are sensitive to inhibitors of poly(ADP-ribose) polymerase (PARP) has spurred the development of cancer therapies that use these inhibitors to target deficiencies in homologous recombination Topics: Animals; BRCA1 Protein; Cell Line; CRISPR-Cas Systems; DNA Damage; DNA Repair; DNA Replication; DNA Topoisomerases, Type I; Female; Gene Editing; Genes, BRCA1; Genome; HeLa Cells; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Mice; Neoplasms; Phthalazines; Piperazines; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms; Ribonuclease H; Ribonucleotides; Synthetic Lethal Mutations; Xenograft Model Antitumor Assays	2018
PARP1 expression, activity and ex vivo sensitivity to the PARP inhibitor, talazoparib (BMN 673), in chronic lymphocytic leukaemia. Oncotarget, 2015, Dec-22, Volume: 6, Issue:41 In chronic lymphocytic leukemia (CLL), mutation and loss of p53 and ATM abrogate DNA damage signalling and predict poorer response and shorter survival. We hypothesised that poly (ADP-ribose) polymerase (PARP) activity, which is crucial for repair of DNA breaks induced by oxidative stress or chemotherapy, may be an additional predictive biomarker and a target for therapy with PARP inhibitors.We measured PARP activity in 109 patient-derived CLL samples, which varied widely (192 - 190052 pmol PAR/10⁶ cells) compared to that seen in healthy volunteer lymphocytes (2451 - 7519 pmol PAR/10⁶ cells). PARP activity was associated with PARP1 protein expression and endogenous PAR levels. PARP activity was not associated with p53 or ATM loss, Binet stage, IGHV mutational status or survival, but correlated with Bcl-2 and Rel A (an NF-kB subunit). Levels of 8-hydroxy-2'-deoxyguanosine in DNA (a marker of oxidative damage) were not associated with PAR levels or PARP activity. The potent PARP inhibitor, talazoparib (BMN 673), inhibited CD40L-stimulated proliferation of CLL cells at nM concentrations, independently of Binet stage or p53/ATM function.PARP activity is highly variable in CLL and correlates with stress-induced proteins. Proliferating CLL cells (including those with p53 or ATM loss) are highly sensitive to the PARP inhibitor talazoparib. Topics: Adult; Antineoplastic Agents; Area Under Curve; Biomarkers, Tumor; DNA Damage; Enzyme-Linked Immunosorbent Assay; Female; Humans; In Situ Hybridization, Fluorescence; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Phthalazines; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; ROC Curve; Sensitivity and Specificity	2015

Article

Year

CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions.

Nature, 2018, Volume: 559, Issue:7713

The observation that BRCA1- and BRCA2-deficient cells are sensitive to inhibitors of poly(ADP-ribose) polymerase (PARP) has spurred the development of cancer therapies that use these inhibitors to target deficiencies in homologous recombination

Topics: Animals; BRCA1 Protein; Cell Line; CRISPR-Cas Systems; DNA Damage; DNA Repair; DNA Replication; DNA Topoisomerases, Type I; Female; Gene Editing; Genes, BRCA1; Genome; HeLa Cells; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Mice; Neoplasms; Phthalazines; Piperazines; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Prostatic Neoplasms; Ribonuclease H; Ribonucleotides; Synthetic Lethal Mutations; Xenograft Model Antitumor Assays

2018

PARP1 expression, activity and ex vivo sensitivity to the PARP inhibitor, talazoparib (BMN 673), in chronic lymphocytic leukaemia.

Oncotarget, 2015, Dec-22, Volume: 6, Issue:41

In chronic lymphocytic leukemia (CLL), mutation and loss of p53 and ATM abrogate DNA damage signalling and predict poorer response and shorter survival. We hypothesised that poly (ADP-ribose) polymerase (PARP) activity, which is crucial for repair of DNA breaks induced by oxidative stress or chemotherapy, may be an additional predictive biomarker and a target for therapy with PARP inhibitors.We measured PARP activity in 109 patient-derived CLL samples, which varied widely (192 - 190052 pmol PAR/10⁶ cells) compared to that seen in healthy volunteer lymphocytes (2451 - 7519 pmol PAR/10⁶ cells). PARP activity was associated with PARP1 protein expression and endogenous PAR levels. PARP activity was not associated with p53 or ATM loss, Binet stage, IGHV mutational status or survival, but correlated with Bcl-2 and Rel A (an NF-kB subunit). Levels of 8-hydroxy-2'-deoxyguanosine in DNA (a marker of oxidative damage) were not associated with PAR levels or PARP activity. The potent PARP inhibitor, talazoparib (BMN 673), inhibited CD40L-stimulated proliferation of CLL cells at nM concentrations, independently of Binet stage or p53/ATM function.PARP activity is highly variable in CLL and correlates with stress-induced proteins. Proliferating CLL cells (including those with p53 or ATM loss) are highly sensitive to the PARP inhibitor talazoparib.

Topics: Adult; Antineoplastic Agents; Area Under Curve; Biomarkers, Tumor; DNA Damage; Enzyme-Linked Immunosorbent Assay; Female; Humans; In Situ Hybridization, Fluorescence; Leukemia, Lymphocytic, Chronic, B-Cell; Male; Middle Aged; Phthalazines; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Poly(ADP-ribose) Polymerases; ROC Curve; Sensitivity and Specificity

2015