Published online 18 April 2009
Haematologica, Vol 94, Issue 6, 861-864 doi:10.3324/haematol.2008.003715
Copyright © 2009 by Ferrata Storti Foundation
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Brief Reports

The level of BCR-ABL1 kinase activity before treatment does not identify chronic myeloid leukemia patients who fail to achieve a complete cytogenetic response on imatinib

Jamshid Sorouri Khorashad, Simon Wagner, Liat Greener, David Marin, Alistair Reid, Dragana Milojkovic, Hetal Patel, Shaun Willimott, Katy Rezvani, Gareth Gerrard, Sandra Loaiza, John Davis, John Goldman, Junia Melo, Jane Apperley, Letizia Foroni

Department of Haematology, Imperial College London, Hammersmith Hospital, London, UK

Correspondence: Jamshid Sorouri-Khorashad, Department of Haematology, Hammersmith Hospital, Imperial College London W12 0NN, London, United Kingdom. E-mail:jamshid.sorouri-khorashad06{at}imperial.ac.uk

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.

Key words: CD34, CML, p-Crkl, imatinib.