title: ATM is usually rearranged in T-cell prolymphocytic leukaemia.
abstract: T-prolymphocytic leukaemia (T-PLL) is a rare, sporadic leukaemia similar to a mature T-cell leukaemia seen in some patients with Ataxia Telangiectasia (A-T), a recessive multisystem disorder caused by mutations of the ATM gene at chromosome 11q23. ATM sequence mutations have been 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 ATM locus in a panel of eight cases, two of which had 11q23 abnormalities. As expected, nucleotide changes were detected in some samples. Two remission samples were wild type. To test for structural lesions, DNA fibres were hybridized with a contig of four labelled cosmids spanning the ATM locus. In all samples there were structural lesions and in four samples both alleles were affected. This provides strong evidence for our suggestion that ATM acts as a tumour suppressor 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 mechanism of inactivation appeared to be unusual because multiple structural lesions on one allele were often observed.
authors.affiliation: Academic Department of Haematology and Cytogenetics, Institute of Cancer Research-Royal Marsden Hospital NHS Trust, London, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Yuille
authors.forename: L J
authors.initials: LJ
authors.lastname: Coignet
authors.forename: S M
authors.initials: SM
authors.lastname: Abraham
authors.forename: F
authors.initials: F
authors.lastname: Yaqub
authors.forename: L
authors.initials: L
authors.lastname: Luo
authors.forename: E
authors.initials: E
authors.lastname: Matutes
authors.forename: V
authors.initials: V
authors.lastname: Brito-Babapulle
authors.forename: I
authors.initials: I
authors.lastname: Vorechovský
authors.forename: M J
authors.initials: MJ
authors.lastname: Dyer
authors.forename: D
authors.initials: D
authors.lastname: Catovsky
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm / Q000032:analysis*; D004268:DNA-Binding Proteins; D006801:Humans; D015463:Leukemia, Prolymphocytic / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics*; D013601:T-Lymphocytes; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases