Good early treatment response in childhood acute lymphoblastic leukemia is associated with Bax nuclear accumulation and PARP cleavage.
BACKGROUND
Bax activation and intracellular redistribution as well as its prognostic significance during steroid-induced apoptosis of leukemic cells in childhood acute lymphoblastic leukemia (ALL) remain a matter of controversy. The purpose of this study was to assess time-resolved changes in Bax activation and its intracellular distribution as well as the percentage of apoptotic cells evaluated by PARP cleavage in response to prednisone treatment in childhood ALL.


METHODS
The study comprised 43 children with de novo ALL. Bax activation and PARP cleavage were measured by laser scanning cytometry in peripheral blood mononuclear cells collected prior to and 6 and 12 hours after prednisone administration.


RESULTS
The mean pretreatment proportion of p89 PARP-positive cells was 3.5%. Six and twelf hours after prednisone administration it increased significantly (p<0.01) only in the group of good treatment responders. A significant rise (p<0.05) in cytoplasmic Bax expression was seen in the good responders as early as 6 hours after prednisone administration followed by a significant rise in Bax nuclear expression after 12 hours. At the same time points the mean percentage of apoptotic cells as well as Bax expression in the cytoplasm and nucleus remained unchanged in the group of poor responders.


CONCLUSIONS
Increased Bax nuclear accumulation (and possibly also aggregation) together with increased PARP cleavage observed within 12 hours after prednisone oral administration were associated with and may predict good outcome in children with newly diagnosed ALL.
Urasiński
Tomasz
T
Clinic of Pediatrics, Hematology, and Oncology, Pomeranian Medical University, Szczecin, Poland. urasin@ams.edu.pl
Urasińska
Elzbieta
E
Grabarek
Jerzy
J
Fydryk
Janusz
J
Domagała
Wenancjusz
W
D000293:Adolescent; D002467:Cell Nucleus / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D016650:Fluorescein-5-isothiocyanate; D005453:Fluorescence; D006801:Humans; D007223:Infant; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D011241:Prednisone / Q000627:therapeutic use; D016896:Treatment Outcome; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
D051028:bcl-2-Associated X Protein; D011065:Poly(ADP-ribose) Polymerases; D016650:Fluorescein-5-isothiocyanate; D011241:Prednisone