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Disease Markers
Volume 30, Issue 5, Pages 221-227
http://dx.doi.org/10.3233/DMA-2011-0777

α-Defensin 1-3 And α-Defensin 4 as Predictive Markers of Imatinib Resistance and Relapse in CML Patients

Gabriel Etienne,1,2 Maryse Dupouy,1 Patricia Costaglioli,3 Claudine Chollet,4 Valérie Lagarde,1 Jean-Max Pasquet,1 Josy Reiffers,2 Bertrand Garbay,3 François-Xavier Mahon,1,4 and Béatrice Turcq1

1Laboratoire Hématopoïèse Leucémique et Cibles Thérapeutiques, INSERM U876, Université Victor Segalen Bordeaux 2, Bordeaux, France
2Institut Bergonié, Centre Régional de Lutte Contre le Cancer de Bordeaux et du Sud-Ouest, Bordeaux, France
3Université de Bordeaux, IPB, EA 4135, ENSTBB, Bordeaux, France
4Laboratoire Hématologie, Hôpital Haut-Lévêque, CHU de Bordeaux, Bordeaux, France

Received 28 June 2011; Accepted 28 June 2011

Copyright © 2011 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective: Imatinib mesylate is a tyrosine kinase inhibitor used as first line treatment in chronic myeloid leukaemia. Despite a remarkable effectiveness, treatment failure cases have been reported in 20 percent of CML patients. The identification of biomarkers which can predict the response to imatinib is our point of interest.

Methods: Gene expression profiling microarray was carried out on secondary imatinib resistant patients. Longitudinal studies were performed on imatinib treated responder/resistant patients. Then, Q-RT/PCR studies were realized on patients prior imatinib initiation.

Results: For imatinib responder patients, we observed a strong and lasting decrease of α-defensin 1-3 and α-defensin 4 expression. For relapse patients, we observed a dramatic increase of α-defensin 1-3 and α-defensin 4 expression before BCR-ABL transcript increase. Moreover, before imatinib initiation, α-defensin 1-3 and α-defensin 4 expression was significantly lower in the resistant group than in the responder group.

Conclusion The variation of expression of α-defensin 1-3 and α-defensin 4 in peripheral blood is associated with imatinib resistance and may reflect an adequate immune control of the disease. Monitoring of α-defensin 1-3 and α-defensin 4 could be helpful to predict the patients who are not going to respond to the treatment.