Transcriptional profiling of ICL670 treated K562 cells

Iron plays a central role in the regulation of many cellular functions. Dysregulation of its metabolism leads an iron overload situation and iron depletion leads to an inhibition of cell proliferation. Recent reports demonstrated that ICL670 (Novartis) acts as a potent NF-kappa-B inhibitor and improves hematological data in a subset of MDS patients (Cilloni et al, Haematologica, s1: 238, 2007). However, the precise mechanism of anti-cancer effect of ICL670 is still uncertain. To evaluate the effect of ICL670, and to identify the moleclular pathways responsible for the observed reduced transfusion requirement during chelation therapy, we performed gene expression profiling to focus on the pathway involved in the anti-cancer effect of ICL670. A human myeloid leukemia cell line, K562, was incubated with or without ICL670 for 16hrs.Gene expression profiling was done using an Affymerix GeneChip (U133 Plus 2.0). Statistical analysis was done by GeneSifter vizXlab, Seattle, WA).