The BCR-ABL gene in chronic myeloid leukemia stem cells has a tendency to quickly mutate, and this may help explain why patients are predisposed to resistance to drugs like imatinib that target that gene, according to a study in the May 2 Journal of the National Cancer Institute.
Treatment with imatinib causes clinical remissions in most patients with chronic myeloid leukemia, but relapses are common and the cancer can become resistant to the drug. The oncogene, BCR-ABL, is the cause of chronic myeloid leukemia. Researchers have hypothesized that the relapses are due to chronic myeloid leukemia stem cells with specific BCR-ABL gene mutations that make them resistant to the drug long before they are exposed to it.
Xiaoyan Jiang, M.D, Ph.D., and Connie Eaves, Ph.D., of the British Columbia Cancer Agency in Vancouver, and colleagues isolated chronic myeloid leukemia stem cells from patients and analyzed them to identify mutations in the BCR-ABL gene.
The stem cells were found to be genetically unstable and had a high frequency of mutations, even in the absence of imatinib. The researchers identified more than 70 BCR-ABL mutations in the stem cells and their immediate progeny, many of which would be expected to alter the BCR-ABL protein, the target of imatinib. This could result in resistance to the drug.