Significance of p53 mutations in patients with chronic lymphocytic leukemia - A sequential study of 30 patients

BACKGROUND. In patients with B-cell chronic lymphocytic leukemia (CLL), con siderable disease heterogeneity within clinical stages necessitates the sea rch for relevant prognostic indicators, particularly those that may help to determine the need for early therapeutic intervention. In the current stud y, the authors investigated the role of p53 mutations and chromosomal abnor malities in 30 patients with CLL. METHODS. Thirty patients were screened for p53 mutations. Half of the group had aggressive disease characterized by leucocytosis, lymph node enlargeme nt, organomegaly, and shortened tumor doubling time. Because 95% of p53 mut ations reside in "hot-spot" regions of exons 5-9 of the p53 gene, the autho rs sequenced these exons completely for mutation detection. RESULTS. Sequence analysis identified p53 mutations in 14 of 30 patients th at were distributed equally among patients with aggressive disease and nona ggressive disease. There were six mutations in exon 7, five mutations in ex on 5, and one mutation each in exons 6 and 8. Five of 15 patients with clin ically aggressive disease had mutations in exon 7. Only one patient with no naggressive disease had an exon 7 mutation. Abnormal cytogenetics were pres ent in 22 of 30 patients (73%). Most patients with the p53 mutation (13 of 14 patients; 93%) displayed abnormal cytogenetics. Twelve of 15 patients wi th aggressive disease and 9 of 15 patients with average disease exhibited a bnormal karyotypes. CONCLUSIONS. The presence of p53 mutations did not predict clinical behavio r or disease outcome, although the frequency of mutations appears to be hig her than reported previously. In this study, mutations of exon 7 (5 of 6 pa tients) occurred in patients with clinically aggressive disease. The signif icance of this observation warrants further examination. (C) 2001 American Cancer Society.