The role of serial BCR-ABL transcript monitoring in predicting the emergence of BCR-ABL kinase mutations in imatinib-treated patients with chronic myeloid leukemia.

BCR-ABL kinase mutations may confer resistance to imatinib in patients with chronic myeloid leukemia (CML), and may predict a poor outcome. We investigated whether rises in BCR-ABL transcript levels predicted mutation development in 82 CML patients receiving imatinib. Eleven mutations were detected in 10 patients. A single 2-fold or greater rise in BCR-ABL transcript did not predict mutations. However, a mutation was detectable in five of six cases with progressively rising levels of transcripts. In contrast, consecutive rises were not seen in any of 33 stable responders. Rising BCR-ABL transcript levels can identify patients who developBCR-ABLmutations. A serial rise is more reliable than a single rise.