title: Investigation on the role of the ATM gene in chronic myeloid leukaemia.
abstract: Chronic myeloid leukaemia (CML) is characterised by an indolent, chronic phase (CP) preceding an acute transformation to blast crisis (BC). While the BCR-ABL fusion oncogene is strongly implicated in the CP, the molecular changes underlying BC are largely unknown. The ataxia telangiectasia gene, ATM, is a candidate gene for this transformation because the complex karyotypes associated with BC of CML suggest that DNA double-strand break repair is defective and because the ABL pathway involves the interaction between the Abl and the Atm proteins. We performed a mutational analysis for ATM in CML using genomic DNA from 14 CML cell lines and 59 CML patients in BC. No clearly deleterious nucleotide changes were observed. A new polymorphism C4138T was discovered which results in a non-conservative amino acid substitution (H1380Y). This variant lies in the Atm recognition motif for the Abl protein. While ATM is unlikely to contribute substantially to CML, further investigation of the H1380Y substitution should clarify whether it has any functional effect.
authors.affiliation: Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London, UK.
authors.forename: J V
authors.initials: JV
authors.lastname: Melo
authors.forename: A
authors.initials: A
authors.lastname: Kumberova
authors.forename: A G
authors.initials: AG
authors.lastname: van Dijk
authors.forename: J M
authors.initials: JM
authors.lastname: Goldman
authors.forename: M R
authors.initials: MR
authors.lastname: Yuille
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D001483:Base Sequence; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics*; D008969:Molecular Sequence Data; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases