title: B-lymphoblastic leukemia/lymphoma: overexpression of nuclear DNA repair protein PARP-1 correlates with antiapoptotic protein Bcl-2 and complex chromosomal abnormalities.
abstract: Poly(ADP-ribose) polymerase-1 (PARP-1) and Bcl-2 are emerging as therapeutic targets in various cancers. The former is a DNA repair protein associated with genomic stability and apoptosis, whereas the latter is an antiapoptotic protein having a DNA repair function through inhibition of PARP-1. Because genomic stability is critical for prognosis in B-lymphoblastic leukemia/lymphoma (B-ALL), we studied the expression of PARP-1 and Bcl-2 proteins in patients with B-ALL of different ages and compared the results with cytogenetic data. The PARP-1 protein was overexpressed in about two-thirds (61%) of patients with B-ALL. It had a nuclear location, whereas Bcl-2 protein was cytosolic. Expression of the 2 proteins showed a highly positive correlation (ρ = 0.367; P < .001). Overexpression of PARP-1 correlated with a complex karyotype (P = .030), and this correlation remained significant for coexpression of PARP-1 and Bcl-2 proteins (χ(2) = 7.498; P = .024) as well as after exclusion of pediatric patients (n = 9, P = .042). Overexpression of PARP-1 was not significantly more common in diploid versus aneuploid karyotypes (50% versus 59%, P = .610). The PARP-1 protein showed no correlation with specific chromosomal abnormalities associated with prognosis in B-ALL, as defined by the World Health Organization. In conclusion, high expression of the PARP-1 protein among patients with B-ALL is related to a complex karyotype and Bcl-2 positivity. Although these findings require validation in a larger population, the observations will be valuable in planning therapeutic trials (such as of PARP inhibitors and BH3 mimetics).
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Calgary and Calgary Laboratory Services (CLS), Calgary, Alberta, Canada T2N 2T9.
authors.forename: Payam
authors.initials: P
authors.lastname: Pournazari
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Canada T2N 2T9.
authors.forename: Ruth F
authors.initials: RF
authors.lastname: Padmore
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Calgary and Calgary Laboratory Services (CLS), Calgary, Alberta, Canada T2N 2T9.
authors.forename: Farid
authors.initials: F
authors.lastname: Kosari
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Canada T2N 2T9.
authors.forename: Peter
authors.initials: P
authors.lastname: Scalia
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Calgary and Calgary Laboratory Services (CLS), Calgary, Alberta, Canada T2N 2T9.
authors.forename: Meer-Taher
authors.initials: MT
authors.lastname: Shahbani-Rad
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Calgary and Calgary Laboratory Services (CLS), Calgary, Alberta, Canada T2N 2T9.
authors.forename: Sami
authors.initials: S
authors.lastname: Shariff
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Calgary and Calgary Laboratory Services (CLS), Calgary, Alberta, Canada T2N 2T9.
authors.forename: Douglas J
authors.initials: DJ
authors.lastname: Demetrick
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Calgary and Calgary Laboratory Services (CLS), Calgary, Alberta, Canada T2N 2T9.
authors.forename: Mark
authors.initials: M
authors.lastname: Bosch
authors.affiliation: Department of Pathology & Laboratory Medicine, University of Calgary and Calgary Laboratory Services (CLS), Calgary, Alberta, Canada T2N 2T9. Electronic address: adnan.mansoor@cls.ab.ca.
authors.forename: Adnan
authors.initials: A
authors.lastname: Mansoor
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases
keywords: B-lymphoblastic leukemia/lymphoma; Bcl-2; Chromosomal abnormalities; PARP-1; Prognosis