title: PARP-1 expression in CD34+ leukemic cells in childhood acute lymphoblastic leukemia: relation to response to initial therapy and other prognostic factors.
abstract: Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear protein that impacts DNA repair and apoptosis. Both experimental and ongoing clinical studies indicate that PARP-1 inhibitors are potent and promising anticancer agents. However, the outcome of treatment with PARP-1 inhibitors depends on the expression of PARP-1 protein in the tumor cells. This study aimed to assess PARP-1 expression in peripheral blood CD34+ leukemic cells before and after 12 hours of prednisone administration as well as the relation between PARP-1 expression and early treatment response to initial therapy and other prognostic factors (immunophenotype, age, initial peripheral blood white blood count [WBC], and risk factor group). The study comprised 43 children with de novo ALL. Cytospins of peripheral blood were stained with mouse anti-CD34-FITC and anti-PARP-1 antibody followed by goat anti-mouse APC-conjugated antibody. DNA was counterstained with PI (propidium iodide). Cellular fluorescence was measured by a laser scanning cytometer. Statistically significant differences in baseline PARP-1 expression with respect to early treatment response (good vs. poor), ALL immunophenotype (ALL B vs. ALL T), age (children < 1 years and > 6 years vs. children 1-6 years), initial WBC (< 20 000/µl vs. ≥ 20 000/µl), and risk factor group (SR vs. IR vs. HR) were not found. PARP-1 expression was increased 12 hours after treatment in poor early treatment responders, whereas it remained statistically unchanged with respect to ALL immunophenotype, age, initial WBC, risk factor group and early treatment response. The overexpression of PARP-1 in poor early treatment responders suggests that it may contribute to treatment failure in this group of children with ALL. Our observation - if confirmed by other studies - may form the rationale for administration of PARP inhibitors in selected subsets of ALL children.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Kruk
authors.forename: Tomasz
authors.initials: T
authors.lastname: Ociepa
authors.forename: Tomasz
authors.initials: T
authors.lastname: Urasiński
authors.forename: Jerzy
authors.initials: J
authors.lastname: Grabarek
authors.affiliation: Elżbieta Urasińska MD, PhD, Department of Pathology, Pomeranian Medical University, Unii Lubelskiej St. 1, 71-252 Szczecin, Poland, tel. +48 91 487 00 32, e-mail: elzura@pum.edu.pl.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Urasińska
mesh_terms: D000293:Adolescent; D018952:Antigens, CD34 / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D016130:Immunophenotyping; D007223:Infant; D008297:Male; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000378:metabolism*; D011379:Prognosis; D012074:Remission Induction
chemical_list: D018952:Antigens, CD34; D014408:Biomarkers, Tumor; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases