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The level of BCR-ABL1 kinase activity before treatment does not identify CML patients who fail to achieve a complete cytogenetic response on Imatinib

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posted on 10.02.2016, 09:41 by J. S. Khorashad, Simon David Wagner, L. Greener, D. Marin, A. G. Reid, D. Milojkovic, H. Patel, S. Willimott, K. Rezvani, G. Gerrard, S. Loaiza, J. G. Davis, J. M. Goldman, J. V. Melo, J. F. Apperley, L. Foroni
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.

History

Citation

Haematologica, 2009, 94, pp. 861-864

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Cancer Studies and Molecular Medicine

Version

VoR (Version of Record)

Published in

Haematologica

Publisher

Ferrata Storti Foundation with European Hematology Association

issn

0390-6078

eissn

1592-8721

Acceptance date

05/02/2009

Copyright date

2009

Available date

10/02/2016

Publisher version

http://www.haematologica.org/content/94/6/861.short

Language

en

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