Individual Research Of Chronic Myelogenous Leukemia Genotyping And Observation Of Nilotinib Clinical Curative Effect

Objective1. For a joint quantitative detecting of four prognosis-related gene in chronic myeloidleukemia (CML) patients to evaluate the feasibility of monitoring and treatmentevaluation gene during imatinib treatment for CML, and verify the feasibility andaccuracy of the prognosis gene for the method of imatinib treatment; And analyzed thecorrelation of BCR/ABL gene mutation in CML patients during imatinib treatment andclinical efficacy.2. To observe the clinical effect of nilotinib on CML cases which were resistance orintolerance of imatinib therapy.Method1. Detecting the expression level of the prognosis-related gene BMI1, CD7, PR3andELA2in138cases CML patients bone marrow by SYBR Green dye real-timefluorescence reverse transcriptase polymerase chain reaction (RT-PCR);and ABLkinase domain of BCR/ABL allele was amplified,followed by direct sequencing andsequence homology analysis to determine the existence of mutation.2.14CML cases treated with nilotinib400mg BID,28d for a course of treatment.Observed the hematology and genetics remission rate and record the occurrence of sideeffects of cases treated with nilotinib. Results1. After imatinib treatment at a single time point,the BMI1, CD7, PR3and ELA2geneexpress level of the relatively high and low is not obvious related with clinical efficacy in patientswith CML, no statistical significance.2. In the sequence analysis of the ABL kinase domain mutations, point mutations werefound in9of138patients(10types), the Y264C, H396R, E459K, E255V, E258V,S481Y, M351T, E282V, E334V, F359V for1case each,which2cases (2.4%,2/83) inearly chronic phase (ECP),6cases (13.3%,6/45) in late chronic phase (LCP),1cases(14.3%,1/7) in accelerated phase(AP).3patients with Y264C, H396R and E459Kmutations（12.5%,3/24）were failure of imatinib treatment, imatinib treatment of theother patients（5.3%,6/114）is effective.3. In the14case of imatinib-resistant CML patients,9cases(64.3%)achieved CHR,4cases(28.6%)relapse after remission.3cases(21.4%)were in complete genetic remission,4cases(28.6%)were the main genetic remission, of which1case(7.1%)in3months afterthe relapse.14cases of CML patients with median follow-up time for3months, with atotal survival rate was92.9%, the median follow-up time of6months the survival rateof71.6%of the total. The grade of nilotinib adverse reactions is mostlyⅠ~Ⅱ, thepatients are generally well tolerated and self-limiting.Conclusion1. The BMI1, ELA2, PR3, and CD7gene expression of the relative level after imatinibtreatment at a single time point cannot serve as prognosis genetic parameters for theimatinib treatment of CML, if you want to these genes as a prognostic gene criteria, itrequired to obtain pre-treatment and treatment two (or more) time monitoring data, andcombine those data from multiple genes to establish comprehensive criteria. 2. ABL kinase point mutation is one of the important mechanisms for the failure ofimatinib treatment; mutation detection rate in LCP patients is higher than ECP.Therefore, imatinib treatment should be applied as soon as possible when CMLdiagnosis, and regular monitoring of the ABL kinase domain point mutations will helpto predict imatinib efficacy and adjust the treatment plan earlier.3. Different types and sites of mutation caused different resistance, and not all pointmutations will lead to the occurrence of drug resistance.4. Nilotinib is an effective drug for the failure of imatinib and not appropriate of bonemarrow transplant in patients with CML, which have a higher remission rate ofhematology/genetics and well tolerated.