Recently the p16 and related p15 genes have been described as candidat
e tumour suppressors at chromosome 9p21. These genes have been found t
o be homozygously deleted at a high frequency in several types of soli
d tumours and also in acute lymphoid leukaemias. In order to determine
whether these genes are more widely involved in haematological malign
ancies, we have investigated a total of 84 samples that did not have h
omozygous p16 or p15 deletions from patients with acute lymphoid leuka
emia (n = 13), acute myeloid leukaemia (n = 24) and chronic myeloid le
ukaemia in blast crisis (n = 43) as well as four haemopoietic cell lin
es. p15 and p16 exon 1 and exon 2 were amplified by polymerase chain r
eaction (PCR), analysed by single-stranded conformation polymorphism (
SSCP) and subsequently by sequencing. Within the p16 gene, a G --> A p
olymorphism at nucleotide 436 was found in 3/80 (4%) leukaemias and th
e cell line HL60. This cell line had also a C --> T mutation at nucleo
tide 232 which causes a premature stop codon. Analysis of the p15 gene
revealed a C --> A mutation within the noncoding sequence 27 nucleoti
des upstream of exon 2 in 10/80 (13%) cases. These data show that inac
tivation of either the p15 or p16 gene by point mutation is a very unc
ommon event in acute leukaemias.