Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Neoplasia Residual/diagnóstico , Proteínas de Fusão bcr-abl/genética , Humanos , Cinética , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Masculino , Pessoa de Meia-Idade , MutaçãoRESUMO
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.
Assuntos
Proteínas de Fusão bcr-abl/genética , Glucuronidase/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Proteínas Proto-Oncogênicas c-abl/genética , Microglobulina beta-2/genética , Adulto , Idoso , DNA Complementar/genética , Feminino , Regulação Leucêmica da Expressão Gênica , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Masculino , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Neoplásico/análise , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
Kinetics of BCR-ABL transcript levels were determined in 19 patients with chronic myeloid leukemia (CML) treated with imatinib for chronic (CP) or accelerated phase (AP). Patients could be divided into three groups with: (1) a sharp and sustained decrease in BCR-ABL transcript level reaching 0.1-0.002% (only CP); (2) an early BCR-ABL overexpression up to 2500% (only AP); and (3) a stable trend with BCR-ABL values between 10 and 100% (CP, AP). In group 1, relapses were not developed within the follow-up; in group 2, patients progressed to blast crisis; in group 3, BCR-ABL overexpression appeared after 12 months in some patients and disease relapses were found 2-16 weeks later. It is summarized that BCR-ABL transcript kinetics clearly characterize responses to imatinib treatment and are highly predictive for disease progression.
Assuntos
Antineoplásicos/uso terapêutico , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Piperazinas/uso terapêutico , Pirimidinas/uso terapêutico , Transcrição Gênica/efeitos dos fármacos , Adulto , Idoso , Benzamidas , Crise Blástica/genética , Feminino , Proteínas de Fusão bcr-abl/efeitos dos fármacos , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
We monitored DLI treatment of 13 post-SCT relapses using quantitative competitive (QC) RT-PCR for BCR-ABL (sensitivity 10(-5)) and compared responses to DLI alone and DLI in combination with interferon-alpha (IFN). Ten relapses (one blast crisis, five cytogenetic and four molecular) were treated with DLI+IFN, three relapses (one cytogenetic, two molecular) were treated with DLI alone. Except the patient treated in blast crisis, who died, all the patients treated with DLI+IFN achieved complete molecular remission, with the median time interval of 3.9 months (range 0.25-10.5 months). None of the three patients treated with DLI alone have achieved complete molecular remission up to now, i.e. 32, 45, and 50 months after DLI. However, in all of them some decrease of BCR-ABL transcript level was detected. Although the retrospective analyses did not confirm that IFN improved the response to DLI, our results based on sensitive molecular monitoring suggest that DLI effect, at least in some patients, is supported by IFN administration.