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author:("differs, joy")
1.  ATRA-induced upregulation of Beclin 1 prolongs the life span of differentiated acute promyelocytic leukemia cells 
Autophagy  2011;7(10):1108-1114.
Acute promyelocytic leukemia (APL) results from a blockade of granulocyte differentiation at the promyelocytic stage. All-trans retinoic acid (ATRA) induces clinical remission in APL patients by enhancing the rapid differentiation of APL cells and the clearance of PML-RARα, APL's hallmark oncoprotein. In the present study, we demonstrated that both autophagy and Beclin 1, an autophagic protein, are upregulated during the course of ATRA-induced neutrophil/granulocyte differentiation of an APL-derived cell line named NB4 cells. This induction of autophagy is associated with downregulation of Bcl-2 and inhibition of mTOR activity. Small interfering RNA-mediated knockdown of BECN1 expression enhances apoptosis triggered by ATRA in NB4 cells but does not affect the differentiation process. These results provide evidence that the upregulation of Beclin 1 by ATRA constitutes an anti-apoptotic signal for maintaining the viability of mature APL cells, but has no crucial effect on the granulocytic differentiation. This finding may help to elucidate the mechanisms involved in ATRA resistance of APL patients, and in the ATRA syndrome caused by an accumulation of mature APL cells.
PMCID: PMC3242613  PMID: 21691148
APL; Beclin 1; apoptosis; ATRA; autophagy; differentiation
2.  α-Defensin 1-3 And α-Defensin 4 as Predictive Markers of Imatinib Resistance and Relapse in CML Patients 
Disease markers  2011;30(5):221-227.
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.
PMCID: PMC3825081  PMID: 21734341
Chronic myeloid leukaemia; imatinib resistance; α-defensin; predictive biomarker

Results 1-2 (2)