Optimising chronic myeloid leukaemia therapy in the face of resistance to tyrosine kinase inhibitors - A synthesis of clinical and laboratory data

Irvine, D. A., Heaney, N. B. and Holyoake, T. L. (2010) Optimising chronic myeloid leukaemia therapy in the face of resistance to tyrosine kinase inhibitors - A synthesis of clinical and laboratory data. Blood Reviews, 24(1), pp. 1-9. (doi: 10.1016/j.blre.2009.11.002)

Abstract

The introduction of imatinib, a tyrosine kinase inhibitor (TKI) that targets the BCR-ABL protein, has revolutionised the treatment of chronic myeloid leukaemia (CML), producing high rates of response that have been durable in many patients. However, because of intrinsic or acquired mechanisms of imatinib resistance, in addition to the persistence of leukaemic stem cells that are resistant to imatinib-induced apoptosis, imatinib treatment does not appear to be curative. Cytogenetic and molecular monitoring enable the identification of patients showing signs of treatment failure and can be used to guide choices regarding subsequent therapeutic options, including imatinib dose escalation, treatment with a secondary TKI or, in selected cases, allogeneic stem cell transplant (allo-SCT). Although these alternative therapies may overcome imatinib resistance, long-term remission or cure from CIVIL is likely to require development of novel interventions that effectively eliminate CML stem cells (Ph+HSC). (c) 2009 Elsevier Ltd. All rights reserved

• Item Type: Articles
• Keywords: Apoptosis BCR-ABL MUTATIONS BJP BLAST-CRISIS CML BLOOD CANCER CANCER STEM-CELLS CELLS Chronic CHRONIC MYELOGENOUS LEUKEMIA CHRONIC-PHASE CML COMPLETE CYTOGENETIC RESPONSE DOMAIN MUTATIONS Drug resistance EUROPEAN-LEUKEMIANET FAILURE IDENTIFICATION IMATINIB MESYLATE THERAPY INHIBITOR INTERVENTION Leukaemia LONG-TERM MECHANISM Myeloid NILOTINIB FORMERLY AMN107 PROTEIN Protein kinase inhibitors RESISTANCE STANDARD-DOSE IMATINIB Stem cells THERAPY Treatment tyrosine kinase inhibitors
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Holyoake, Professor Tessa and Irvine, Dr David and Heaney, Dr Nicholas
• Authors: Irvine, D. A., Heaney, N. B., and Holyoake, T. L.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: Blood Reviews
• ISSN: 0268-960X