alpha-defensin 1-3 and alpha-defensin 4 as predictive markers of imatinib resistance and relapse in CML patients.

摘要

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 alpha-defensin 1-3 and alpha-defensin 4 expression. For relapse patients, we observed a dramatic increase of alpha-defensin 1-3 and alpha-defensin 4 expression before BCR-ABL transcript increase. Moreover, before imatinib initiation, alpha-defensin 1-3 and alpha-defensin 4 expression was significantly lower in the resistant group than in the responder group. CONCLUSION: The variation of expression of alpha-defensin 1-3 and alpha-defensin 4 in peripheral blood is associated with imatinib resistance and may reflect an adequate immune control of the disease. Monitoring of alpha-defensin 1-3 and alpha-defensin 4 could be helpful to predict the patients who are not going to respond to the treatment.