Journal of Clinical Oncology, Vol 15, 1158-1162, Copyright © 1997 by American Society of Clinical Oncology
Altered expression of p53 and mdm-2 proteins at diagnosis is associated with early treatment failure in childhood acute lymphoblastic leukemia
DI Marks, BW Kurz, MP Link, E Ng, JJ Shuster, SJ Lauer, D Carroll, I Brodsky and DS Haines
Department of Medicine, Allegheny University of the Health Sciences, Philadelphia, PA 19102, USA.
PURPOSE: To determine whether potential alteration in p53 function through
p53 gene mutation or mdm-2 overexpression correlates with early treatment
failure in childhood acute lymphoblastic leukemia (ALL). PATIENTS AND
METHODS: Diagnostic marrow samples from 34 children were analyzed for p53
gene alterations by western blot and SSCP/DNA sequence analysis and for
mdm-2 overexpression by western blot analysis. These samples were derived
from two groups of children with ALL: 17 good outcome patients who are in
long-term continuous complete remission and 17 poor outcome patients who
did not achieve a complete remission or relapsed within 6 months of
achieving remission. RESULTS: Two children within the poor outcome group
were found to have p53 gene mutations. Furthermore, five poor outcome
patients were shown to have greater than 10-fold overexpression of mdm-2
protein compared with the mean level of mdm-2 protein measured in the good
outcome group. Aberrant p53 protein expression was found in only one good
outcome patient, whereas no good outcome children were found to have
elevated levels (> 10-fold) of mdm- 2 protein. CONCLUSION: We show for
the first time that potential alteration in p53 function in childhood ALL
is more common (P = .036) in cases of early treatment failure than in
children who remain in long- term continuous remission.
