INVERSE CORRELATION BETWEEN LOSS OF HETEROZYGOSITY OF THE SHORT ARM OF CHROMOSOME-12 AND P15(INK4B) P16(INK4) GENE INACTIVATION IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA/

Seventy-four patients with acute lymphoblastic leukaemia (ALL) were an alysed with limited allelotyping to detect loss of heterozygosity on c hromosome segments 6q, 9p, 12p and 13q in order to detect patterns of genetic alteration. In the case of chromosome 9, analyses were also pe rformed to detect inactivation of the p15(ink4B) and p16(ink4) genes b y Southern blot and sequencing techniques. The deletion data from thes e chromosomes were correlated to each other and to clinical features i ncluding prognosis. Allelic loss of these chromosomal regions could be detected in 24% (6q), 15% (12p) and 10% (13q) of the patients respect ively, whereas aberrations involving 9p were detected in approximately 50% of the cases. There was an inverse correlation between loss of he terozygosity (LOH) for chromosome 12 and inactivation of the p16(ink4) gene. This finding may suggest that a leukaemogenic event on chromoso me 12p affects the same pathway of cell-cycle control as p16(ink4) ina ctivation or, alternatively, reflects the fact that these mutations te nd to occur in cells of different lineages.