ATM IS USUALLY REARRANGED IN T-CELL PROLYMPHOCYTIC LEUKEMIA

T-prolymphocytic leukaemia (T-PLL) is a rare, sporadic leukaemia simil ar to a mature T-cell leukaemia seen in some patients with Ataxia Tela ngiectasia (A-T), a recessive multisystem disorder caused by mutations of the ATM gene at chromosome 11q23., ATM sequence mutations have bee n reported in 46% of T-PLL cases, but some cases also have karyotypic abnormalities at 11q, including 11q23., This led us to investigate the structure of the A TM locus in a panel of eight cases, two of which h ad 11q23 abnormalities, As expected, nucleotide changes were detected in some samples, Two remission samples were wild type, To test for str uctural lesions, DNA fibres were hybridized with a contig of four labe lled cosmids spanning the A TM locus, In all samples there were struct ural lesions and in four samples both alleles were affected, This prov ides strong evidence for our suggestion that ATM acts as a tumour supp ressor during T-PLL tumorigenesis. Some additional role for ATM during T-PLL tumorigenesis is possible since nucleotide changes were present in addition to structural lesions disrupting both alleles. The mechan ism of inactivation appeared to be unusual because multiple structural Lesions on one allele were often observed,.