%0 Journal Article
%T Prediction of response to therapy with ezatiostat in lower risk myelodysplastic syndrome
%A Naomi Galili
%A Pablo Tamayo
%A Olga B Botvinnik
%A Jill P Mesirov
%A Margarita R Brooks
%A Gail Brown
%A Azra Raza
%J Journal of Hematology & Oncology
%D 2012
%I BioMed Central
%R 10.1186/1756-8722-5-20
%X RNA was available on 30 patients enrolled in the trial and analyzed for gene expression on the Illumina HT12v4 whole genome array according to the manufacturer¡¯s protocol. Gene marker analysis was performed. The selection of genes associated with the responders (R) vs. non-responders (NR) phenotype was obtained using a normalized and rescaled mutual information score (NMI).We have shown that an ezatiostat response profile contains two miRNAs that regulate expression of genes known to be implicated in MDS disease pathology. Remarkably, pathway analysis of the response profile revealed that the genes comprising the jun-N-terminal kinase/c-Jun molecular pathway, which is known to be activated by ezatiostat, are under-expressed in patients who respond and over-expressed in patients who were non-responders to the drug, suggesting that both the biology of the disease and the molecular mechanism of action of the drug are positively correlated.
%U http://www.jhoonline.org/content/5/1/20/abstract