Project name: Homo sapiens

Description: We had previously demonstrated an increased proapoptotic effect of Imatinib (STI571) in combination with Amifostine (AMI) in K562 cell line. In this study we used genomic scale gene expression profiling to monitor changes at transcriptional level in K562 cells during the treatment with AMI+STI571. We identified a transcriptional repressor of survival genes, known as BTF, which triggers a pro-apoptotic signal, potentially helpful to overcome the resistance to STI571. This finding could be particularly useful to design novel therapeutic strategies for leukaemia patients.Keywords: PharmacogenomicOverall design: cRNA from Control and Treated K562 cells were mixed in equal amounts and incubated with a microarray slide for hybridisation. RNA from six independent paired experiments was subjected to transcriptional profiling.To identify a list of genes that best distinguishes the joint effect of the two drugs from what might be predicted on the basis of their effects alone, we decided to apply a class of experimental design named multifactorial design, as described by Y.H. Yang and T. Speed (15). If we let C denote mRNA that is derived from the untreated cells (Control), and A and S denote mRNA that is derived from the cells that were treated by AMI and STI571 separately, we can then use AS to denote cells that were treated with both drugs simultaneously. Since our main interest was to identify gene variations due to the drug interaction (named “AS effect”), experimental design that offers the best precision, is a balance of direct and indirect comparison.

Data type: Transcriptome or Gene expression

Sample scope: Multiisolate

Relevance: Medical

Release date: 2006-03-01

Last updated: 2005-09-15