The t(9;22)(q34;q11) chromosomal translocation,nominated as the Philadelphia chromosome,generates the BCR-ABL fusion gene.In the presence of haematologic features of a chronic myeloproliferative disorder,the detection of this chromosomal abnormality establishes the diagnosis of chronic myeloid leukaemia.The biology of CML has enabled pioneering studies with targeted therapies,i.e.imatinib.Inhibition of BCR-ABL with imatinib results in high levels of efficacy in patients with newly diagnosed CML in chronic phase (CP),but an estimate of 35% of patients could benefit from more effective treatment primarily because of resistance but also because of toxicity.Because of this,several novel treatment strategies are being investigated both in the second line setting but also in newly diagnosed CML-CP.These strategies include treatment with next-generation tyrosine kinase inhibitors,such as dasatinib,nilotinib,or bosutinib,which also target BCR-ABL but with increased in vitro potency compared with imatinib,and possibly a reduced potential for resistance.Modified imatinib regimens are also being investigated in newly diagnosed CML-CP,including higher doses and combination with alternative classes of agent,such as interferon.Existing data suggest that both newer agents and combination approaches can improve treatment responses compared with standard imatinib treatment,although further data is needed,particularly from ongoing phase 3 trials,before the standard of care is revised.