ABSTRACT
OBJECTIVE: Of 140 chronic myeloid leukemia patients responding to imatinib with complete cytogenetic remission, 32 exhibited a plateau of BCR-ABL values at >or=0.1% level in a minimum of three subsequent samples (minimal duration, 6 - 9 months). Median follow-up of unchanged BCR-ABL transcript level was 12 months (range, 6 - 64). We tested this group of patient for BCR-ABL mutations to reveal resistance development and to evaluate the risk of disease progression. MATERIALS AND METHODS: Altogether, 134 samples of peripheral blood of these 32 patients were tested for mutation in BCR-ABL kinase domain. RESULTS: Mutation was detected by direct sequencing in 9 of 32 patients (28%). Loss of complete cytogenetic remission or 1 log rise of BCR-ABL was observed in five of nine patients at a median of 5 months (range, 4-17) since first detection of mutation. One patient with no mutation relapsed 12 months after the start of the BCR-ABL plateau. In 5 of 32 patients without mutation (16%), BCR-ABL level significantly decreased after the first plateau to levels that stayed unchanged for a median of 11 months (range, 7-28). CONCLUSION: We show here that the BCR-ABL constant levels >or=0.1% (BCR-ABL plateau) in imatinib-responding patients may indicate mutation analysis. This approach highly reduces the number of examinations for mutation in chronic myeloid leukemia responders and may present cost-effective alternative applicable in clinical practice.
Subject(s)
Antineoplastic Agents/therapeutic use , Cytogenetic Analysis , Fusion Proteins, bcr-abl/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Mutation , Piperazines/therapeutic use , Pyrimidines/therapeutic use , RNA, Messenger/genetics , Adult , Aged , Benzamides , Female , Humans , Imatinib Mesylate , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Male , Middle Aged , Remission Induction , Reproducibility of ResultsSubject(s)
Fusion Proteins, bcr-abl/analysis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Reverse Transcriptase Polymerase Chain Reaction/methods , Reverse Transcriptase Polymerase Chain Reaction/standards , Fusion Proteins, bcr-abl/genetics , Genes, abl , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosisSubject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Neoplasm, Residual/diagnosis , Fusion Proteins, bcr-abl/genetics , Humans , Kinetics , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/genetics , Male , Middle Aged , MutationABSTRACT
We compared the effect of control genes (CG): total Abelson (total-ABL), beta-2-microglobulin (B2M) and beta-glucuronidase (GUS), recommended in the Europe Against Cancer (EAC) program, on real-time BCR-ABL monitoring in patients with chronic myeloid leukemia (CML). We focused on the stability of CG expressions during therapy and the effect of the CGs on BCR-ABL ability to characterize the disease status and disease prognosis, issues that have not been addressed yet. The results showed B2M as a very convenient CG for BCR-ABL monitoring. On the contrary, the widely used total-ABL was not confirmed as appropriate for normalization of gene expression in CML.