title: PARP1-driven apoptosis in chronic lymphocytic leukemia.
abstract: Chronic lymphocytic leukemia (CLL) is considered a malignancy resulting from defects in apoptosis. For this reason, targeting apoptotic pathways in CLL may be valuable for its management. Poly [ADP-ribose] polymerase 1 (PARP1) is the main member of a family of nuclear enzymes that act as DNA damage sensors. Through binding on DNA damaged structures, PARP1 recruits repair enzymes and serves as a survival factor, but if the damage is severe enough, its action may lead the cell to apoptosis through caspase activation, or necrosis. We measured the PARP1 mRNA and protein pretreatment levels in 26 patients with CLL and the corresponding posttreatment levels in 15 patients after 3 cycles of immunochemotherapy, as well as in 15 healthy blood donors. No difference was found between the pre- and posttreatment levels of PARP1, but we found a statistically significant relative increase of the 89 kDa fragment of PARP1 that is cleaved by caspases in the posttreatment samples, indicating PARP1-related apoptosis in CLL patients after treatment. Our findings constitute an important step in the field, especially in the era of PARP1 inhibitors, and may serve as a base for future clinical trials with these agents in CLL.
authors.affiliation: Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece.
authors.forename: Panagiotis T
authors.initials: PT
authors.lastname: Diamantopoulos
authors.affiliation: Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Sofotasiou
authors.affiliation: Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Papadopoulou
authors.affiliation: Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece.
authors.forename: Katerina
authors.initials: K
authors.lastname: Polonyfi
authors.affiliation: Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece.
authors.forename: Theodoros
authors.initials: T
authors.lastname: Iliakis
authors.affiliation: Department of Internal Medicine, Hematology Unit, Laikon General Hospital, National and Kapodistrian University of Athens, 11527 Athens, Greece.
authors.forename: Nora-Athina
authors.initials: NA
authors.lastname: Viniou
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics*; D004249:DNA Damage / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis / Q000235:genetics*; D059748:Proteolysis
chemical_list: C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases