Peter Rohoň, Edgar Faber, Ivana Skoumalová, Karel Indrák
Chronic myeloid leukemia (CML) is the chronic myeloproliferative disease characterized by the presence of Philadelphia chromosome (Ph) and/or BCR/ABL fusion gene. Imatinib mesylate (Glivec®) is developed as the first molecularly targeted therapy that specifically inhibits the Bcr/Abl tyrosine kinase. Imatinib becomes first-line treatment for patients with newly diagnosed CML in chronic phase. Nevertheless, resistance to the drug has been frequently reported and it presents dominant problem in 20 % of CML patients after 5 years of treatment. Point mutations within Abl kinase domain are the major cause of resistance. In other patients the resistance is caused by overexpression of Bcr/Abl protein, novel acquired cytogenetic aberrations and by drug level in target cells. The major causes of resistance to imatinib are analyzed in this review.