本文選題：急性B淋巴細(xì)胞白血病 + 髓源性抑制細(xì)胞��； 參考：《遵義醫(yī)學(xué)院》2016年碩士論文

【摘要】：目的:髓源性抑制細(xì)胞(myeloid-derived suppressor cells,MDSC)是近年發(fā)現(xiàn)的一種具有免疫抑制功能的細(xì)胞,參與腫瘤的免疫逃逸,促進(jìn)腫瘤生長。目前國內(nèi)外對于MDSC的研究主要集中在荷瘤小鼠和成人實(shí)體瘤,白血病方面僅有個(gè)別報(bào)道。本課題旨在通過研究急性B淋巴細(xì)胞白血病(acute B lymphoblastic leukemia,B-ALL)患兒外周血中MDSC數(shù)目、亞群比例、主要功能物質(zhì)變化,以及對NK細(xì)胞的影響,探討MDSC在兒童B-ALL發(fā)病中的作用,有助于進(jìn)一步闡明兒童ALL的發(fā)病機(jī)制,并為制定相關(guān)的免疫靶向治療提供理論依據(jù)。方法:收集初診治療前和完全緩解后B-ALL患兒及健康兒童外周血,采用流式細(xì)胞術(shù)(FCM)檢測各組外周血中MDSC(CD11b+CD33+)的數(shù)量變化;兩種不同亞群:單核細(xì)胞樣MDSC(CD14+CD11b+CD33+)和粒細(xì)胞樣MDSC(CD15+CD11b+CD33+)的比例及其變化情況;以及MDSC主要功能物質(zhì)精氨酸酶1(Arg-1)和活性氧物質(zhì)(ROS)的表達(dá)情況;同時(shí)檢測各組外周血中NK細(xì)胞活化所必需的表面受體NKG2D的表達(dá)水平。結(jié)果:1.治療前B-ALL患兒外周血中MDSC數(shù)量比例(2.41%±0.45%)明顯高于完全緩解組(1.56%±0.44%)及正常組(0.68%±0.16%)(F=92.094,P0.01);且MDSC數(shù)量比例與不同危險(xiǎn)度分層呈正相關(guān)(r s=0.680,P0.01),即MDSC數(shù)量比例隨危險(xiǎn)度分層升高而增加,不同危險(xiǎn)度分層間MDSC的數(shù)量比例差異也具有統(tǒng)計(jì)學(xué)意義(F=23.360,P0.01);治療前B-ALL外周血MDSC亞群以粒細(xì)胞樣MDSC(G-MDSC)為主,完全緩解后B-ALL患兒與正常對照外周血中MDSC亞群組成無明顯差別,且均以單核細(xì)胞樣MDSC(M-MDSC)為主。2.外周血MDSC中Arg-1和ROS的在治療前B-ALL患兒表達(dá)最高(41.00%±9.34%;3004.26±611.05),完全緩解后次之(24.13%±5.49%;2031.75±294.01),正常對照組表達(dá)最低(10.72%±4.37%;811.33±195.12)(F=95.285,P0.01;F=124.089,P0.01);Arg-1的表達(dá)隨ALL危險(xiǎn)度分層升高有上升趨勢,但差異無統(tǒng)計(jì)意義(F=1.373,P=0.265);不同危險(xiǎn)度分層中ROS表達(dá)具有統(tǒng)計(jì)學(xué)差異(F=6.363,P0.01),其中高危組表達(dá)明顯高于中危組和標(biāo)危組,中危和標(biāo)危組的表達(dá)差異無統(tǒng)計(jì)學(xué)意義。3.B-ALL患兒外周血NK中NKG2D的比例在治療前(21.35%±5.94%)和完全緩解后(14.28%±4.59%)均明顯低于正常對照(35.51%±5.25%)(F=78.589,P0.01),且與MDSC數(shù)量比例呈負(fù)相關(guān)(r=㧟0.558,P0.01),隨MDSC數(shù)量增加而降低。結(jié)論:1.MDSC在B-ALL患兒外周血中數(shù)量增加,且危險(xiǎn)度分層越高增加越明顯,其治療前亞群以G-MDSC為主,在治療后MDSC的數(shù)量降低,亞群組成趨于正常,以M-MDSC為主。2.MDSC兩種主要功能物質(zhì)Arg-1和ROS在治療前B-ALL患兒中表達(dá)最高,完全緩解后明顯下降但仍高于正常兒童。3.B-ALL患兒外周血NK細(xì)胞中NKG2D的比例明顯低于正常且與MDSC數(shù)量比例呈負(fù)相關(guān)。4.B-ALL患兒中MDSC數(shù)量、亞群以及主要功能物質(zhì)均發(fā)生明顯變化,同時(shí)伴有NK細(xì)胞功能下降,本研究結(jié)果提示MDSC可能通過抑制機(jī)體免疫功能,增加腫瘤的免疫逃逸從而參與兒童B-ALL的發(fā)病。
[Abstract]:Objective: Myeloid-derived suppressor cells (MDSCs) is an immunosuppressive cell found in recent years, which participates in the immune escape of tumor and promotes tumor growth. At present, the research on MDSC is mainly focused on tumor-bearing mice and adult solid tumors, leukemia is only reported. The purpose of this study was to investigate the role of MDSC in the pathogenesis of B-ALL in children with acute B lymphocyte leukemia (ACL) by studying the number of MDSC, the proportion of subsets, the changes of main functional substances and the effect on NK cells in the peripheral blood of children with acute B lymphoblastic leukemia. It is helpful to elucidate the pathogenesis of ALL in children and provide theoretical basis for the development of immunoreactive therapy. Methods: the peripheral blood of children with B-ALL and healthy children were collected before and after initial treatment and complete remission. Flow cytometry (FCM) was used to detect the quantity of MDSC(CD11b CD33 in peripheral blood of each group. Two different subgroups: monocyte-like MDSC(CD14 CD11b CD33) and granulocyte-like MDSC(CD15 CD11b CD33 (MDSC(CD15 CD11b CD33), and the expression of argininase 1 (Arg-1) and reactive oxygen species (Ros) in MDSC; At the same time, the expression of NKG2D, which is necessary for NK cell activation, was detected. The result is 1: 1. Before treatment, the proportion of MDSC in peripheral blood of children with B-ALL was 2.41% 鹵0.45%) significantly higher than that of complete remission group (1.56% 鹵0.44%) and normal group (0.68% 鹵0.160.094%, P 0.01), and there was a positive correlation between MDSC quantity and different risk stratification, that is, the proportion of MDSC increased with the increase of risk stratification. Before treatment, the MDSC subsets in peripheral blood of B-ALL were mainly granulocyte-like MDSC-G-MDSC.There was no significant difference in MDSC subgroup between children with B-ALL and normal controls after complete remission. The monocyte like MDSCM-MDSCM-MDSC2 was the main one. The expression of Arg-1 and ROS in peripheral blood MDSC was the highest in children with B-ALL before treatment (41.00% 鹵9.34), followed by 24.13% 鹵5.493.75 鹵294.01% after complete remission. The lowest expression of Arg-1 and ROS in normal control group was 10.72% 鹵4.37%. The expression of Arg-1 was increased with the increase of ALL risk stratification. However, there was no statistical significance in the expression of ROS in different risk stratification. The expression of ROS in high risk group was significantly higher than that in middle risk group and standard risk group. There was no significant difference in the expression of NK NKG2D between the middle risk group and the standard risk group. 3. The percentage of NK NKG2D in peripheral blood of children with moderate risk and standard risk group was 21.35% 鹵5.94% before treatment and 14.28% 鹵4.59% after complete remission. It was significantly lower than that of normal control group (35.51% 鹵5.2558% 鹵78.589P 0.01a), and negatively correlated with the ratio of MDSC. Conclusion: 1. The number of MDSC in peripheral blood of children with B-ALL increased, and the higher the risk stratification, the more obvious. The subgroup of MDSC was mainly G-MDSC before treatment. After treatment, the number of MDSC decreased and the subgroup became normal. 2. The expression of Arg-1 and ROS, two main functional substances of MDSC, were the highest in children with B-ALL before treatment. After complete remission, the percentage of NKG2D in peripheral blood NK cells in children with complete remission was significantly lower than that in normal children. 3. The percentage of NKG2D in peripheral blood NK cells was significantly lower than that in normal children and negatively correlated with the proportion of MDSC. The results suggest that MDSC may play a role in the pathogenesis of B-ALL in children by inhibiting the immune function of the body and increasing the immune escape of the tumor.
【學(xué)位授予單位】：遵義醫(yī)學(xué)院
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2016
【分類號】：R733.71

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