Abnormalities of the p53 gene in juvenile myelomonocytic leukaemia

Juvenile chronic myelomonocytic leukaemia (JMML) is a rare myeloproliferati ve disorder of childhood. Fewer than 30% of cases of JMML terminate in a bl ast crisis: however, its molecular mechanism is unknown. Since mutation and /or deletion of the p53 gene has been reported to be associated with diseas e progression in a wide variety of human cancers, including adult-type chro nic myelogenous leukaemia, we studied the p53 gene in 20 patients with JMML (16 samples in chronic phase and seven at blast crisis). Exons 4-8 of the p53 gene, which cover all the hot spots of point mutations, were amplified by the polymerase chain reaction (PCR) method and subjected to mutation scr eening by single-strand conformation polymorphism analysis. No mobility shi ft of single-strand DNA of PCR products in polyacrylamide gel electrophores is, indicating point mutations, was found in 19/20 patients, DNA of the rem aining patient in the chronic phase failed to be amplified by PCR and South ern blot analysis with XbaI-digested genomic DNA revealed a gross rearrange ment (presumed deletion) of the p53 gene. These data indicate that abnormal ities of the p53 gene are rare in JMML, and not responsible for acute trans formation, but could be involved in the pathogenesis of some cases of JMML.