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.
Wang
Lihui
L
Department of Haematology, Royal Liverpool University Hospital, Prescot St, Liverpool L7 8XP, United Kingdom.
Knight
Katy
K
Lucas
Claire
C
Clark
Richard E
RE
D001549:Benzamides; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D016044:Fusion Proteins, bcr-abl / Q000235:genetics*; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D010770:Phosphotransferases / Q000235:genetics; D010879:Piperazines / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011743:Pyrimidines / Q000627:therapeutic use*; D012334:RNA, Neoplasm / Q000097:blood*
D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012334:RNA, Neoplasm; D000068877:Imatinib Mesylate; D010770:Phosphotransferases; D016044:Fusion Proteins, bcr-abl