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Title: The level of BCR-ABL1 kinase activity before treatment does not identify CML patients who fail to achieve a complete cytogenetic response on Imatinib
Authors: Khorashad, J. S.
Wagner, Simon David
Greener, L.
Marin, D.
Reid, A. G.
Milojkovic, D.
Patel, H.
Willimott, S.
Rezvani, K.
Gerrard, G.
Loaiza, S.
Davis, J. G.
Goldman, J. M.
Melo, J. V.
Apperley, J. F.
Foroni, L.
First Published: Jun-2009
Publisher: Ferrata Storti Foundation with European Hematology Association
Citation: Haematologica, 2009, 94, pp. 861-864
Abstract: Imatinib is currently the first line therapy for newly diagnosed patients with chronic myeloid leukemia. However, 20–25% of patients do not achieve durable complete cytogenetic responses. The mechanism underlying this primary resistance is unknown, but variations in BCR-ABL1 kinase activity may play a role and can be investigated by measuring the autophosphorylation levels of BCR-ABL1 or of a surrogate target such as Crkl. In this study we used flow cytometry to investigate the in vitro inhibition of Crkl phosphorylation by imatinib in CD34+ cells in diagnostic samples from two groups of patients distinguished by their cytogenetic response. No difference in inhibition of Crkl phosphorylation was observed in the two groups. The observation that increasing the dose of imatinib in vivo did not increase the level of cytogenetic response in some non-responders suggests that in at least a proportion of patients imatinib resistance may be due to activation of BCR-ABL1-independent pathway.
DOI Link: 10.3324/haematol.2008.003715
ISSN: 0390-6078
eISSN: 1592-8721
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © 2009 Ferrata Storti Foundation. This is an open-access paper. Obtained from the Haematologica Journal website Deposited with reference to the publisher’s archiving policy available on the SHERPA/RoMEO website.
Appears in Collections:Published Articles, Dept. of Cancer Studies and Molecular Medicine

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