State-of-the-art in the treatment of chronic myeloid leukaemia.
OBJECTIVE
To revise the current goals of therapy of chronic myeloid leukaemia and to incorporate the influence of the underlying chronic myeloid leukaemia biology on directing therapeutic management.


RESULTS
The management of chronic myeloid leukaemia has been revolutionized by targeted molecular therapy that inhibits the ABL kinase activity of the BCR-ABL gene. The achievement of a major molecular response with the first tyrosine kinase inhibitor to be introduced into clinical practice, imatinib, is a focus of therapeutic regimens. Second-generation tyrosine kinase inhibitors are available that have more potent effects than imatinib, and have activity against imatinib-resistant subclones. Strategies to overcome the restoration of BCR-ABL signalling and subsequent resistance to therapy include imatinib dose escalation, a more potent tyrosine kinase inhibitor, as well as non-BCR-ABL-dependent approaches and agents in clinical development.


CONCLUSIONS
Therapeutic advances in chronic myeloid leukaemia continue to circumvent the challenges of drug resistance and the minimal residual leukaemic burden providing effective strategies for future therapy.
Department of Haematology, The Hammersmith Hospital, London, UK. d.milojkovic@imperial.ac.uk
Dragana
D
Milojkovic
Jane
J
Apperley
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001549:Benzamides; D019008:Drug Resistance, Neoplasm; D016044:Fusion Proteins, bcr-abl / Q000037:antagonists & inhibitors / Q000378:metabolism; D016313:Genes, abl; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000378:metabolism; D009154:Mutation; D010879:Piperazines / Q000494:pharmacology / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use; D013234:Stem Cells / Q000378:metabolism; D014184:Transplantation, Homologous
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D016044:Fusion Proteins, bcr-abl; C498826:nilotinib