Background: The role of human multidrug resistance gene (MDR1) SNPs in the interindividual variability of imatinib mesylate (IM) response has received considerable attention. We aimed to study the association between ...Background: The role of human multidrug resistance gene (MDR1) SNPs in the interindividual variability of imatinib mesylate (IM) response has received considerable attention. We aimed to study the association between SNPs of the MDR1 gene (C1236T, G2677T/A, C3435T) and IM response in chronic myeloid leukemia (CML) patients. Method: A retrospective case-control study was conducted on 48 patients with CML undergoing IM therapy. All patients were genotyped using PCR-RFLP method. Results: The genotype and allele frequencies of C1236T and C3435T were not significantly different between CML patients responders and non-responders to IM (p > 0.05). The frequencies of 2677T allele and 2677TT genotype were significantly increased in CML patients IM responders which as compared with IM non-responders (50% vs 26.9%, p = 0.013 and 27.3% vs 3.8%, p = 0.029 respectively). Whereas the 2677AA genotype and CAC haplotype were found only in CML patients IM non-responders (15.4%). Conclusion: Pretreatment genotyping of G2677A/T appears to be useful for predicting IM resistance, which may allow the best choice of drug treatment for CML patients.展开更多
Imatinib is the standard first line treatment for chronic myeloid leukemia(CML).Owing to doserelated toxicities of Imatinib such as neutropenia,there is scope for treatment optimization through therapeutic drug monito...Imatinib is the standard first line treatment for chronic myeloid leukemia(CML).Owing to doserelated toxicities of Imatinib such as neutropenia,there is scope for treatment optimization through therapeutic drug monitoring(TDM).Trough concentration of 1g/mL is considered the therapeutic threshhold.Existing methods for the detection of Imatinib in plasma are limited by long read out time and expensive instrumentation.Hence,Raman spectroscopy was explored as a rapid and objective tool for monitoring Imatinib concentration.Three approaches:conventional Raman spectroscopy(CRS),Drop coating deposition Raman(DCDR)spectroscopy and surface-enhanced Raman spectroscopy(SERS)were employed to detect the required trough concentration of 1g/mL and above.Detection of therapeutically relevant concentrations(1g/mL)using SERS and suitable nanoparticle substrates has been demonstrated.Prospectively,rigorous validation using clinical samples is necessary to confirm the utility of this approach in routine clinical usage.展开更多
文摘Background: The role of human multidrug resistance gene (MDR1) SNPs in the interindividual variability of imatinib mesylate (IM) response has received considerable attention. We aimed to study the association between SNPs of the MDR1 gene (C1236T, G2677T/A, C3435T) and IM response in chronic myeloid leukemia (CML) patients. Method: A retrospective case-control study was conducted on 48 patients with CML undergoing IM therapy. All patients were genotyped using PCR-RFLP method. Results: The genotype and allele frequencies of C1236T and C3435T were not significantly different between CML patients responders and non-responders to IM (p > 0.05). The frequencies of 2677T allele and 2677TT genotype were significantly increased in CML patients IM responders which as compared with IM non-responders (50% vs 26.9%, p = 0.013 and 27.3% vs 3.8%, p = 0.029 respectively). Whereas the 2677AA genotype and CAC haplotype were found only in CML patients IM non-responders (15.4%). Conclusion: Pretreatment genotyping of G2677A/T appears to be useful for predicting IM resistance, which may allow the best choice of drug treatment for CML patients.
文摘Imatinib is the standard first line treatment for chronic myeloid leukemia(CML).Owing to doserelated toxicities of Imatinib such as neutropenia,there is scope for treatment optimization through therapeutic drug monitoring(TDM).Trough concentration of 1g/mL is considered the therapeutic threshhold.Existing methods for the detection of Imatinib in plasma are limited by long read out time and expensive instrumentation.Hence,Raman spectroscopy was explored as a rapid and objective tool for monitoring Imatinib concentration.Three approaches:conventional Raman spectroscopy(CRS),Drop coating deposition Raman(DCDR)spectroscopy and surface-enhanced Raman spectroscopy(SERS)were employed to detect the required trough concentration of 1g/mL and above.Detection of therapeutically relevant concentrations(1g/mL)using SERS and suitable nanoparticle substrates has been demonstrated.Prospectively,rigorous validation using clinical samples is necessary to confirm the utility of this approach in routine clinical usage.
