title: The effects of high dose methylprednisolone on apoptosis in children with acute lymphoblastic leukemia.
abstract: Rapid leukemic cell kill at initial diagnosis of patients with acute lymphoblastic leukemia (ALL) has been shown to be associated with a favorable outcome. The aim of the present study was to investigate the effect of high dose methylprednisolone (HDMP) on in vivo blast cell apoptosis in children with ALL. Annexin V-binding and Fas (CD95), Fas ligand (FasL; CD95L), and Bcl-2 expression in PB blasts were determined in newly diagnosed children with ALL before and 4, 24, 96 h after initiation of HDMP treatment (n=20) or conventional dose steroids (CDS) (n=10) as the control group. A decrease in absolute blast count (from 40.8 x 09 to 21.4 x 109/l) associated with an increase in apoptosis (14.2 to 26.9%) (P < 0.05) was detected 4 h after initiation of HDMP. A significant increase in Fas and FasL expression was detected 96 h after HDMP. There was no significant change in apoptosis, Fas and FasL expression from baseline in the control group treated with CDS. The changes in Bcl-2 expression after treatment was not significant in both groups. The results of this preliminary study have shown that HDMP treatment was effective in inducing immediate (within 4 h) blast cell apoptosis. The contribution of Fas/FasL interaction in the rapid component of cell kill remains to be determined, as the increase in the expression of these molecules was evident later.
authors.affiliation: Division of Paediatric Haematology, Ihsan Dogramac Children's Hospital, Hacettepe University, Ankara, Turkey.duckan@hacettepe.edu.tr
authors.forename: D
authors.initials: D
authors.lastname: Uçkan
authors.forename: S
authors.initials: S
authors.lastname: Yetgin
authors.forename: M
authors.initials: M
authors.lastname: Cetin
authors.forename: E
authors.initials: E
authors.lastname: Ozyürek
authors.forename: H
authors.initials: H
authors.lastname: Okur
authors.forename: D
authors.initials: D
authors.lastname: Aslan
authors.forename: M
authors.initials: M
authors.lastname: Tuncer
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002648:Child; D004305:Dose-Response Relationship, Drug; D004341:Drug Evaluation; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis / Q000096:biosynthesis; D008775:Methylprednisolone / Q000494:pharmacology* / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000473:pathology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000187:drug effects; D019014:fas Receptor / Q000032:analysis / Q000096:biosynthesis
chemical_list: C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D008775:Methylprednisolone