| Objective: imatinib mesylate (IM) of 137 patients with CML patients with molecular therapeutic effect.Methods: The hospital diagnosed Ph + and / or BCR-ABL1 gene plus the CML patients with 137 patients, collect patient sex, age, previous course of the disease at different time points the bone marrow and other clinical data, RT-PCR quantitative detection of BCR-ABL1 gene level; The above information and the related statistical analysis.Results: The median observation time of 36 months, received IM median duration of treatment for the past 3 years, 1 year of interferon therapy; IM 18 months of cumulative CP CMR patients was 82%, 89% for 36 months , with the reported close; AP / BP 18-month cumulative CMR patients was 40%, 45% for 36 months, slightly higher than reported in the literature, IM on the CP, AP / BP patients have a statistically significant effect. Length of CP patients with the first CMR past the time course of the disease, and more than 2 years duration in patients with previous CMR rate decreased, the same effect on patients with previous use of interferon in patients with CMR rate, the results were statistically different.Conclusion: IM of patients with chronic phase CML patients, especially CMR has a good effect, but the effectiveness has not been satisfactory progress in patients; previous course of interferon therapy may affect the use of IM effect on CML-CP patients, the proposed use of IM should be treated as soon as possible, CMR to obtain a higher rate. Objective: 38 cases of CML patients imatinib mesylate resistance and preliminary characterization of its mechanism.Methods: The hospital confirmed the PH + and / or BCR-ABL1 gene + in 38 patients with CML, response to treatment evaluation based on primary or secondary drug resistance; collection of patient age, previous clinical data course, RT-PCR quantitative detection BCR-ABL1 gene level, and determine if patients have BCR-ABL1 kinase domain point mutation; data related to the above statistical analysis.Results: 38 patients were resistant to the standard reference to 2010 European standards, including CP29 patients, AP / BP 9, median observation time of 36 months. 28 cases of primary drug resistance (18 months without the CCR and has not been obtained CMR), including 20 CP, 8 AP / BP patients; secondary resistance in 10 patients (treatment of loss of CMR), 9 CP patients an AP / BP patients; resistant course and interferon therapy in patients with previous time was significantly longer than the continuous CMR, secondary drug resistance in patients (p <0.05); detection means, the 6 patients positive review by the genetic loss of the initial CMR ; mutation detection results suggest that in 21 cases (55.3%) patients ABL kinase fusion gene mutations exist, including P-loop region mutations in 11cases (52.4%), A-loop 2 cases (9.5%), T315I 5 cases (23.8%) other regions: M351T 1 cases, F359L / V in 1 case, these areas are vulnerable to BCR-ABL1 mutant gene and IM combined with reduced ability to produce drug resistance; mutations in patients receiving interferon therapy the median time was 1.45±0.61 years longer than the continuous CMR were 0.72±0.61 years, with significant difference (p <0.05); AP / BP patients and the incidence of CP mutations in patients with a significant difference (p = 0.00024).Conclusion: Although the effects are good, but IM has shown some resistance rate (27.7%); IM before the course and interferon therapy may be involved in the occurrence of drug resistance, suggesting that early treatment may reduce the application of IM resistance rate. BCR-ABL1 gene mutation is the most common mechanism of resistance to IM, mutations mainly in the ATP binding domain; advanced point mutation in patients was significantly higher than the incidence of chronic disease, and the incidence rate of time-related to interferon treatment, suggesting that interferon treatment may result by increasing the mutation rate of occurrence of CML cells to IM resistance. |
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