| Objective To investigate the sensitivity of 54 leukemia-related genes and 81 chemotherapeutic drugs in patients with T-cell acute lymphoblastic leukemia,and to find the drug-resistant genes,and to analyze the clinical significance of the gene.Methods From October 2016 to January 2018,38 patients with newly diagnosed T-ALL were enrolled in the Department of Hematology.Forty-eight patients were given 4-8 ml of peripheral venous blood before the initial treatment.High-throughput sequencing technology was used to detect 54 leukemia-related genes,and the highest mutation rate gene was selected to explore the clinical significance of the gene.At the same time,38 kinds of chemotherapeutic drug susceptibility tests were performed in 38 patients.Each drug was set at three different concentrations of 0.37 uM,1.1uM and 3.3uM to explore the correlation between the gene and drug sensitivity,as well as drug sensitivity and gender.There was no correlation between age,number of white blood cells at the time of initial diagnosis,number of bone marrow blasts,hemoglobin,platelets,and LDH.Then,38 patients were recorded with information about the treatment effect after one course of actual clinical chemotherapy,and the drug sensitivity was compared with the actual clinical effect.Result 1.Among the 54 leukemia-associated genes,the mutation rate of NOTCH1 gene was the highest,18 of 38 patients had NOTCH1 mutation,and 20 had no NOTCH1 mutation.2.In 38 patients with newly diagnosed T-ALL,the platelet level in the mutant groupwas lower than that in the non-mutant group(p<0.05),but the NOTCH1 mutation was between gender,age,white blood cell count,bone marrow blast cell count,LDH level,and hemoglobin level.There was no correlation(p>0.05),suggesting that patients with NOTCH1 mutations had lower platelet counts and increased the risk of bleeding.3.In the 38 patients with newly diagnosed T-ALL,the difference between the NOTCH1 mutation and the sensitivity of three different concentrations of dexamethasone was statistically significant.The mutation group was more resistant to0.37 uM dexamethasone than the non-mutant group.(p=0.000),resistance to 1.1uM dexamethasone was higher than that of non-mutant group(p=0.011),drug resistance to3.3uM dexamethasone was higher than that of non-mutant group(p=0.022),NOTCH1 mutation group Resistance to dexamethasone did not change by increasing the concentration of dexamethasone,suggesting that the NOTCH1 mutation caused dexamethasone resistance.4.0.37 uM and 1.1uM dexamethasone drug sensitivity and age,gender,number of white blood cells at the time of initial diagnosis,bone marrow cells,hemoglobin,platelets were not correlated(p<0.05),LDH and 0.37 uM dexamethasone drugs There was a correlation between sensitivity(p=0.044)and a correlation between LDH and 1.1 uM dexamethasone drug sensitivity(p=0.024).There was no correlation between drug sensitivity of 3.3uM dexamethasone and age,gender,number of white blood cells at the time of diagnosis,bone marrow cells,hemoglobin,platelet,and LDH(p<0.05).Multivariate analysis revealed no association between LDH and dexamethasone drug sensitivity.5.38 patients with newly diagnosed T-ALL were treated according to the VDCLP or VICLP regimen.Of the 18 patients with NOTCH1 mutations,5 had CR1 and 13 had not reached CR1.20 patients with NOTCH1 non-mutation group,16 patients with CR1,Four patients had non-CR1,and the difference between the two groups was statistically significant(p=0.003),indicating that the results of in vitro susceptibilitytesting were consistent with the actual clinical efficacy.Conclusion The NOTCH1 mutation can cause dexamethasone resistance.After increasing the dose of dexamethasone,it still shows drug resistance,which may be a poor prognosis.At the same time,patients with NOTCH1 mutation have low platelet level and bring high bleeding risk. |
