Hematology 2006
© 2006 The American Society of Hematology
Defining and Managing Imatinib Resistance
Michael J. Mauro
Correspondence: Michael J. Mauro MD, Associate Professor, Center for Hematologic Malignancies, Oregon Cancer Institute, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, UHN-73C, Portland, OR 97239 USA; Email: maurom{at}ohsu.edu
Abstract
While imatinib is highly effective therapy, with improving prospects over time for sustained remission and potential to severely limit or eliminate disease progression and transformation, a minority of patients either fail or respond suboptimally to imatinib; as well, disease eradication may not be possible with imatinib. Distinct patterns of resistance have evolved with the use of imatinib, and Abl kinase mutations, which alter imatinib binding or favor kinase conformations inaccessible to imatinib, are a common finding associated with clinical resistance. Dasatinib and nilotinib, alternate Abl kinase inhibitors, restore hematologic and cytogenetic remission in the majority of patients with primary failure or acquired resistance in chronic phase disease; in advanced disease and Philadelphia chromosome (Ph)+ ALL, responses are more limited and relapse is common. Future studies with these agents will focus on further optimizing imatinib response, reduction of minimal residual disease, and prevention of resistance. Still newer inhibitors active against T315I mutant BCR-ABL may overcome primary and secondary resistance to dasatinib and nilotinib.
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Copyright © 2006 by the American Society of Hematology.
