ALTERED EXPRESSION OF P53 AND MDM-2 PROTEINS AT DIAGNOSIS IS ASSOCIATED WITH EARLY TREATMENT FAILURE IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA

Purpose: To determine whether potential alteration in p53 function thr ough p53 gene mutation or mdm-2 overexpression correlates with early t reatment failure in childhood acute lymphoblastic leukemia (ALL). Pati ents and Methods: Diagnostic marrow samples from 34 children were anal yzed for p53 gene alterations by western blot and SSCP/DNA sequence an alysis and for mdm-2 overexpression by western blot analysis. These sa mples were derived from two groups of children with ALL: 17 good outco me patients who are in long-term continuous complete remission and 17 poor outcome patients who did not achieve a complete remission or rela psed within 6 months of achieving remission.Results: Two children with in the poor outcome group were found to have p53 gene mutations. Furth ermore, five poor outcome patients were shown to have greater than 10- fold overexpression of mdm-2 protein compared with the mean level of m dm-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 md m-2 protein. Conclusion: We shaw for the first time that potential alt eration in p53 function in childhood ALL is more common (P = .036) in cases of early treatment failure than in children who remain in long-t erm continuous remission. (C) 1997 by American Society of Clinical Onc ology.