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).