Onkologie. 2008:2(3):150-155

CHRONIC MYELOID LEUKEMIA - FROM MOLECULAR PATHOGENESIS TO TARGETED THERAPY

Peter Rohoň¹, Daniela Žáčková²

¹ Hemato-onkologická klinika FN a LF UP v Olomouci

² Interní hematoonkologická klinika LF MU a FN Brno

Chronic myeloid leukemia (CML) is the myeloproliferative disorder characterized by the presence of Philadelphia chromosome (Ph) and/or BCR/ABL fusion gene. Imatinib mesylate (IM, Glivec®) was developed as the first molecularly targeted therapy that specifically inhibits the Bcr/Abl tyrosine kinase (TK). IM 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 20–30 % of CML patients after 5 years of treatment. Point mutations within Abl kinase domain are regarded as the major cause of resistance. In some patients the resistance is caused by overexpression of Bcr/Abl protein, novel acquired cytogenetic aberrations and by low drug level in leukemic cells. New treatment strategies in case of IM failure in CML patients are focused on overcoming of described mechanisms by new molecules which are more potent Bcr/Abl tyrosine kinase inhibitors (TKI) than imatinib and more effective against imatinib-resistant clones with mutations in Abl kinase domain. Presently, immunotherapy of CML has been studied with regard to first reports on successful use of vaccines. The role of allogenic stem cell transplantation (ASCT) in the TKI era is not unambiguous, the main indication may be limited to TKI-resistant patients.

Keywords: Key words: CML, BCR/ABL fusion gene, resistance to IM, TKI, immunotherapy.

Published: November 1, 2008  Show citation