The Philadelphia (Ph) chromosome, which occurs as a result of a translocation between chromosomes 9 and 22, generates a BCR-ABL fusion oncogene in leukaemia cells. The BCR-ABL fusion protein has constitutive tyrosine kinase activity. The development of imatinib mesylate (STI571, Gleevec®), a potent and selective BCR-ABL tyrosine kinase inhibitor, represents an important advance in cancer therapy. However, inherent mechanisms confer resistance to imatinib mesylate in some leukaemia patients. In order to identify the genes potentially related to these resistance mechanisms, we examined genes differentially expressed in BCR-ABL-positive cell lines resistant to imatinib mesylate. A comparison of global gene expression using the HG-U133 2.0 plus Gene Chip array was first performed. Twenty-three genes were shown to be overexpressed in an imatinib-resistant cell line. Among these, RUNX1T1 was shown to be overexpressed in another resistant cell line and in patients resistant to imatinib mesylate. This suggests that RUNX1T1 is a putative candidate for the further study of imatinib mesylate resistance.

Related Articles