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Type: Artigo de periódico
Title: Molecular Monitoring Of Chronic Myeloid Leukemia Patients Treated With Imatinib Using Real Time Pcr [monitoramento Molecular De Pacientes Com Leucemia Mieloide Crônica Em Uso De Imatinib Através Da Técnica De Pcr Quantitativo Em Tempo Real]
Author: Machado M.P.
Abstract: Chronic myeloid leukemia (CML) is a myeloproliferative disorder characterized by the presence of the Philadelphia chromosome (Ph), the result of a bcr-abl gene fusion, the product of which is a protein with kinase activity that can be inhibited by imatinib. Imatinib is currently the first-line treatment of CML and molecular monitoring of BCR-ABL transcripts is essential to detect early loss of response to treatment. The aim of this study was to standardize the quantitative PCR (RQ-PCR) method for molecular monitoring of BCR-ABL transcripts in patients with CML treated with imatinib. Peripheral blood samples from chronic phase patients were collected for RQ-PCR at diagnosis and every three months after treatment with imatinib. The Taqman method was used for RQ-PCR. A standard curve was constructed with dilutions of 108 to 103 of a plasmid with the b3a2 and b2a2 transcripts and the ABL gene being used as the control gene. Duplicate runs were made. The threshold used was 0.05 and the efficiency was determined at 99%. The results are reported as a BCR-ABL/ABL ratio (%). For the reference baseline value of the laboratory, 30 samples from patients at diagnosis were quantified and the median value was calculated at 83.66%. Major molecular response (MMR) was considered a three log reduction from the baseline value. MMR values were adjusted to international scale, using a conversion factor of 1.19. After standardization, the BCR-ABL levels of 60 chronic phase CMLpatients treated with imatinib were measured at diagnosis and then at every three months. Hematological, major cytogenetic and complete cytogenetic responses were achieved in 57 (95%), 45 (75%) and 38 (63%) patients, respectively. Twenty-four out of 60 patients achieved a MMR (40%) in a median time of 8.5 months. Overall survival was higher for patients with CCR (100%) versus patients with no CCR (77% - p= 0.01) at 48 months. Patients with CCR and with MMR had a higher event free-survival rate compared to patients with CCR and no MMR (p= 0.007). In conclusion, we demonstrated the prognostic impact of achieving CCR and a MMR and also the importance of molecular monitoring in the follow-up of CML patients.
Rights: aberto
Identifier DOI: 
Date Issue: 2010
Appears in Collections:Unicamp - Artigos e Outros Documentos

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