The effects of high dose methylprednisolone on apoptosis in children with acute lymphoblastic leukemia.
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.
Uçkan
D
D
Division of Paediatric Haematology, Ihsan Dogramac Children's Hospital, Hacettepe University, Ankara, Turkey.duckan@hacettepe.edu.tr
Yetgin
S
S
Cetin
M
M
Ozyürek
E
E
Okur
H
H
Aslan
D
D
Tuncer
M
M
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
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor; D008775:Methylprednisolone