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Kesearch Of Clinical Data And Exptession Of Regulatory T-cell Associated Cytokines In Acute Myeloid Leukemia

Posted on:2013-01-03Degree:MasterType:Thesis
Country:ChinaCandidate:H WuFull Text:PDF
GTID:2234330374483586Subject:Internal Medicine
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Part1Research of clinical date of441patients with acute myeloid leukemia from Shandong University Affiliated Qilu HospitalBackground and Objective:Leukemia is one class of hematological malignancy with higher incidence, which seriously impact body’s health, characterized by anemia, infection and bleeding on clinic. Acute myeloid leukemia (AML) is the most common type. In our research, we selected the data of patients with AML from Shandong University affiliated Qilu Hospital in recent10years. Objective explore the epidemiological characterize, trend of hepatitis, style of diagnostic, treatment and prognosis in this area. In order knowing more about the clinical feature, provide theory basis to improve the prevention, diagnosis, treatment and prognosis of AML.Methods:The objects of study are the patients with AML from Shandong University affiliated Qilu Hospital,441cases in total. According to the Wright-Giemsa dying and cell chemical dying characteristics of bone marrow and peripheral blood, all the cases were made a definite diagnosis coincidence with both the tumor and blood type standard in2001from world health organization (WHO) and the French-America-British standard in China. Then we do further analysis of the patients according to the bone marrow morphology, immunology, cytogenetic and molecular results.For Acute Promyelocytic Leukemia (APL) patients, we divided them into two groups:high risk group (WBC≥10×109/L) and low risk group (WBC<10×109/L). Both the high risk group and low risk group accepted the same traditional standard induction therapy. Compare the effect of treatment.For non Acute Promyelocytic Leukemia (non-APL) patients, we also divided them into two groups. One group accepted the traditional two-drug induction therapy; the other accepted the clinic trail of three-drug joint induction chemotherapy. Compare the effect.Statistical analyses were performed using SPSS version17.0software (SPSS, Chicago, IL, USA). T test or variance analysis was used for normal distribution material application. Wilcoxon rank test were used for non-normal distribution material application. P value <0.05was considered statistically significant.Patients were followed by telephone, date up to January2012. Statistic and compare the median survival time.Results:We selected patients with AML,441cases in all. The gender ratio of which is1.33:1. The median age of diagnosis is41year-old. There are104cases for APL and337cases for non-APL according to the FAB system.In the CBC test for the patients of newly diagnosed, without any chemotherapy, about8.8percent of all cases with extremely higher of WBC (WBC≥100×109/L). Most of the cases with lower hemoglobin and platelet count than normal.We have the bone marrow morphology data of all the cases.36.1percent of all cases with cytogenetic data, among these data,50.3percent for normal karyotype,11.3percent for complex karyotype.40.1percent of the cases with molecular immunology data.22.9percent with molecular genetic data.For APL high risk group, the total effective rate of first induction chemotherapy (CR+PR) was68.4percent. No significant difference was found compared with low risk group (74.2percent). For non-APL group, the total effective rate of patient with clinic trail three drug joint induction chemotherapy (HAD, HAA, et al) was86.7percent. Significantly higher than that in traditional two drug induction chemotherapy (43.2percent)(P<0.001).In the follow-up, the median survival time of patients with APL group was35months. Among these,33months for the APL high risk group, compared to36months in APL low risk group. For non-APL group, the median survival time of clinic trail three drug joint induction chemotherapy was17months, significantly higher than that in traditional two drug induction chemotherapy (11months). In the study we found that both high WBC in the first CBC test (WBC≥100×109/L) and complex karyotype in cytogenetic indicated poor prognosis.Conclusion:By analyzing the data of patients with AML clinic in Shandong University Affiliated Qilu Hospital in recent10years, we found the results of epidemiology and FAB style were fairly accorded with experimental results reported in literatures.The first CBC test, the count of hemoglobin, white blood cell and platelet coincided well with literatures. The MICM in bone marrow, some of the results not fit well with the literatures both at home and abroad. But for deep analysis, it means little.For APL group, it has differences between the high risk group and the low risk group both in the effective of chemotherapy and median survival time, but not statistically significant. We consider it requires more literatures and large amount of samples.For non-APL group, it has significantly differences in the effective of chemotherapy and median survival time between the traditional two drug induction chemotherapy group and clinic trail three drug joint induction chemotherapy. It has advantages that three drug joint induction chemotherapy for patients in remission and prognosis, which was supported by literatures and our study.Patients who had high WBC count in the first CBC test and complex karyotype in cytogenetic with poor prognosis. Part2Aberrant expression of Treg associated cytokine IL-35along with IL-10and TGF-P in acute myeloid leukemiaObjectives:Acute myeloid leukemia (AML) is the most common hematological malignancy in adults, characterized by distorted proliferation and the development of myeloid cells and their precursors in the blood and bone marrow. Interleukin35(IL-35), a novel inhibitory cytokine secreted by regulatory T (Treg) cells is a novel potential target used for the therapeutic manipulation of Treg activity in order to treat cancer and autoimmune diseases. To investigate the role and imbalance of Treg-related cytokines in the pathogenesis of AML, we measured the plasma concentration of three Treg-associated cytokines [IL-35, IL-10and transforming growth factor-β (TGF-β)] and evaluated their clinical relevance. The concentration of IL-35, IL-10and TGF-β in plasma specimens from55patients with AML [27newly diagnosed (ND) patients and28in complete remission (CR)] and24controls was analyzed using the enzyme-linked immunosorbent assay method. Significantly higher levels of plasma IL-35and IL-10were observed in AML ND patients compared with healthy controls or AML CR patients. IL-10concentrations were positively correlated with TGF-β, whereas no correlations were found between the other cytokines. IL-10levels were positively correlated with white blood cell (WBC) and neutrophil (NEU) count but there were no correlations between IL-35and TGF-β with WBC and NEU count. In conclusion, we demonstrated for the first time that AML ND patients have increased plasma concentrations of IL-35, suggesting that this cytokine is involved in the pathophysiological process of the disease, and that further research is required to address this issue.Methods:1.Patients and controls:We selected55patients with AML, which divided into acute myeloid leukemia newly diagnostic group (AML ND) and acute myeloid leukemia complete remission (AML CR) group. And24healthy volunteers were studied as control group.2. We applied Enzyme-linked immunosorbent assay (ELISA) to detect the serum level of IL-35, IL-10and TGF-β.3.Statistical analyses were performed using Wilcoxon rank-sum test and the Student’s t-test. Spearman’s test was used for correlation analysis. P value<0.05was considered statistically significant.Results1.Plasma concentrations of IL-35were significantly higher in AML ND patients [median,107.40pg/ml (range,74.95-468.22)] than in AML CR patients [median,68.80pg/ml (range,48.07-252.47); P=0.001]) and control group [median,63.23pg/ml (range,24.46-489.45); P<0.001].2.Plasma IL-10levels were significantly higher in AML ND patients [median,14.41pg/ml (range,6.39-59.20)] than in AML CR patients [median,8.47pg/ml (range,5.78-17.82); P<0.001]) and control group[median,5.87pg/ml (range,(4.29-7.78); P<0.001].3.Plasma concentrations of TGF-β were significantly higher in control group [median,1008.86pg/ml (range,250.28-33793.68)] than in AML ND patients [median,377.31pg/ml (range,83.68-7220.11); P=0.001]) or AML CR patients [median,285.39pg/ml (range,42.54-2172.26); P<0.001].4.Plasma IL-10concentration were positively correlated with plasma TGF-β concentration (r=0.435, P=0.023).Conclusions:1. Plasma concentrations of IL-35were significantly higher in AML patients than in AML CR patients and control group, indicating that IL-35may take part in the pathogenesis of AML. Plasma concentrations of IL-10were significantly higher in AML patients than in AML CR patients and control group, indicating that IL-10may take part in the pathogenesis of AML. Plasma concentrations of TGF-β were significantly lower in AML patients than in control group, indicating that TGF-β may take part in the pathogenesis of AML.2. Plasma IL-10concentration were positively correlated with plasma TGF-P concentration, indicating that IL-10may have a synergistic effect with TGF-β in AML.
Keywords/Search Tags:Acute Myeloid Leukemia, MICM, Induction Chemotherapy, PrognosisIL-35, IL-10, TGF-β
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