Emerging drugs in chronic myelogenous leukaemia
Emerging drugs in chronic myelogenous leukaemia
Chronic myelogenous leukaemia (CML) is characterised by a t(9;22)(q34;q11) translocation, which produces a fusion BCR-ABL protein with constitutive tyrosine kinase activity that is central to the pathogenesis of CML representing an ideal target for therapeutic intervention. Targeting BCR-ABL by imatinib has revolutionised the clinical course of CML. All patients in early chronic phase treated with imatinib achieve a complete haematological response, with 80-90% achieving a complete cytogenetic response. However, BCR-ABL transcripts remain detectable in the great majority of them, and approximately 16% chronic phase CML patients are resistant to or relapse after imatinib treatment, mainly through pre-existing or acquired point mutations in the binding pocket. Thus, other targeted approaches are being developed to overcome imatinib resistance. These include two novel tyrosine kinase inhibitors (nilotinib and dasatinib) that are producing clinical responses in different clinical settings, while other similar compounds are under evaluation in preclinical studies. Furthermore, additive immunotherapeutic strategies are emerging to synergise with imatinib in the elimination of molecular residual disease. This paper reviews the current details regarding these approaches and their developments.
BCR–ABL, chronic myelogenous leukaemia, drug resistance, imatinib, immunotherapy, kinase inhibitor, vaccine
651-664
Bocchia, Monica
55dbb34d-ab5d-4828-a4a4-a1fef1b41bb6
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Lauria, Francesco
f01f163b-abcb-4aad-b952-f4356692f519
November 2006
Bocchia, Monica
55dbb34d-ab5d-4828-a4a4-a1fef1b41bb6
Forconi, Francesco
ce9ed873-58cf-4876-bf3a-9ba1d163edc8
Lauria, Francesco
f01f163b-abcb-4aad-b952-f4356692f519
Abstract
Chronic myelogenous leukaemia (CML) is characterised by a t(9;22)(q34;q11) translocation, which produces a fusion BCR-ABL protein with constitutive tyrosine kinase activity that is central to the pathogenesis of CML representing an ideal target for therapeutic intervention. Targeting BCR-ABL by imatinib has revolutionised the clinical course of CML. All patients in early chronic phase treated with imatinib achieve a complete haematological response, with 80-90% achieving a complete cytogenetic response. However, BCR-ABL transcripts remain detectable in the great majority of them, and approximately 16% chronic phase CML patients are resistant to or relapse after imatinib treatment, mainly through pre-existing or acquired point mutations in the binding pocket. Thus, other targeted approaches are being developed to overcome imatinib resistance. These include two novel tyrosine kinase inhibitors (nilotinib and dasatinib) that are producing clinical responses in different clinical settings, while other similar compounds are under evaluation in preclinical studies. Furthermore, additive immunotherapeutic strategies are emerging to synergise with imatinib in the elimination of molecular residual disease. This paper reviews the current details regarding these approaches and their developments.
This record has no associated files available for download.
More information
Published date: November 2006
Keywords:
BCR–ABL, chronic myelogenous leukaemia, drug resistance, imatinib, immunotherapy, kinase inhibitor, vaccine
Organisations:
Cancer Sciences
Identifiers
Local EPrints ID: 358167
URI: http://eprints.soton.ac.uk/id/eprint/358167
ISSN: 1472-8214
PURE UUID: b76888fe-cdee-4759-9773-f08daed6167f
Catalogue record
Date deposited: 22 Oct 2013 13:02
Last modified: 15 Mar 2024 03:41
Export record
Altmetrics
Contributors
Author:
Monica Bocchia
Author:
Francesco Lauria
Download statistics
Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.
View more statistics
