Mutations of the p53 gene in myelodysplastic syndrome and overt leukaemia

We analysed p53 mutations in 24 patients with myelodysplastic syndrome (MDS) and overt acute myeloid leukaemia after a period of MDS, using polymerase chain reaction-single strand conformation polymorphism analysis. In exons 5 to 8, mobility shifts were detected in five of the 24 patients. Sequence analysis was subsequently performed, and four missense mutations (16.7%) and one silent nucleotide substitution were identified. Patients harbouring mutations were characterized as having advanced disease. Loss of the wild type allele was observed in three of the four patients with missense mutations. No mobility shifts of the N-ras or FMS gene were detected in these four patients. We next analysed the correlation of the p53 mutations with the progression of MDS in three patients. The mutation was accompanied by the progression in two of the three patients. These findings suggest that mutations of the p53 gene are associated with progression in some cases of MDS, while being compatible with stable disease or clonal evolution in others.