P15(INK4B) AND P16(INK4) GENE INACTIVATION IN ACUTE LYMPHOCYTIC-LEUKEMIA

Malignant cells from 52 children with acute lymphocytic leukemia (ALL) were investigated for inactivation of the p15(ink4B) and p16(ink4) genes and other genetic alterations on chromosome 9p21. Homozygous deletions of the p15(ink4B) and/or the p16(ink4) genes were detected in 16 cases and a further 9 cases showed evidence of allelic loss either by hemizygous deletion or loss of heterozygosity (LOH) for 9p21 markers. Most cases had loss of both genes, but 5 patients had lost only p16(ink4) and 2 cases had homozygous loss of p15(ink4B) only. Sequence analysis of all exons of p15(ink4B) and p16(ink4) was performed in patients with hemizygous deletions or LOH for 9p21 markers. A frame shift mutation of p16(ink4) exon 1 was shown in 1 case, whereas all other clones carried the wild-type sequence of p15(ink4B) and p16(ink4) in the remaining allele. The data suggest that both the p15(ink4B) and p16(ink4) genes can be inactivated in ALL. The existence of a hitherto undefined tumor-suppressor gene on chromosome 9p cannot be ruled out. (C) 1995 by The American Society of Hematology.