Investigation on the role of the ATM gene in chronic myeloid leukaemia

Chronic myeloid leukaemia (CML) is characterised by an indolent, chronic ph ase (CP) preceding an acute transformation to blast crisis (BC). While the BCR-ABL fusion oncogene is strongly implicated in the CP, the molecular cha nges underlying BC are largely unknown. The ataxia telangiectasia gene, ATM , is a candidate gene for this transformation because the complex karyotype s 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 cle arly deleterious nucleotide changes were observed. A new polymorphism C4138 T was discovered which results in a non-conservative amino acid substitutio n (H1380Y). This variant lies in the Atm recognition motif for the Abi prot ein. While ATM is unlikely to contribute substantially to CML, further inve stigation of the H1380Y substitution should clarify whether it has any func tional effect.