title: α-defensin 1-3 and α-defensin 4 as predictive markers of imatinib resistance and relapse in CML patients.
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.
  
  
  CONCLUSIONS
  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.
authors: Laboratoire Hématopoïèse Leucémique et Cibles Thérapeutiques, Université Victor Segalen Bordeaux, France.
authors: Gabriel
authors: G
authors: Etienne
authors: Maryse
authors: M
authors: Dupouy
authors: Patricia
authors: P
authors: Costaglioli
authors: Claudine
authors: C
authors: Chollet
authors: Valérie
authors: V
authors: Lagarde
authors: Jean-Max
authors: JM
authors: Pasquet
authors: Josy
authors: J
authors: Reiffers
authors: Bertrand
authors: B
authors: Garbay
authors: François-Xavier
authors: FX
authors: Mahon
authors: Béatrice
authors: B
authors: Turcq
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D015415:Biomarkers / Q000097:blood*; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D008137:Longitudinal Studies; D010456:Peptides, Cyclic / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D010879:Piperazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D023084:alpha-Defensins / Q000097:blood / Q000235:genetics / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D015415:Biomarkers; C429483:DEFA1A3 protein, human; D010456:Peptides, Cyclic; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D023084:alpha-Defensins; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases