p53 mutation in intron 6 as a diagnostic marker for high risk childhood T-lineage acute lymphoblastic leukemia

One hundred and twenty-eight children with acute lymphoblastic leukemia (ALL), 52 T-lineage and 76 B-lineage, were analyzed for the p53 mutation in intron 6, which we have previously identified in diverse childhood malignancies. The mutation, a single base substitution from G to A, 39 base pairs upstream to exon 7, was exclusively identified in the T-lineage ALL patients (6/52; 12%) (p = 0.0082). Five of the 6 patients with the mutation relapsed (83%) compared to 17 out of 46 free of the mutation (37%) (Yates' χ² p = 0.08). The frequency of the mutation in the relapsed group was 23% (5/22). The mutation was detected already at diagnosis in 5 of the 6 patients, in one as a germ line. A significantly lower overall survival of the mutation carriers was observed, 17% at 40 months of follow up compared with 69% in those free of the mutation (p = 0.0057). A significant decrease in relapse free survival was also observed between the two groups (p = 0.0195). We suggest that this mutation may have an important clinical relevance as a useful diagnostic marker for high risk and poor prognosis T-cell ALL in children.