本文選題：IL7R + 急性淋巴細(xì)胞白血病��； 參考：《南京醫(yī)科大學(xué)》2016年碩士論文

【摘要】：第一部分 IL7R在成人急性淋巴細(xì)胞白血病中的突變、表達(dá)及其臨床意義目的：IL-7R (interleukin-7 receptor)是IL-7的受體。IL-7R由IL-7Ra(由IL7R編碼)和γc組成。本研究旨在探討成人急性淋巴細(xì)胞白血病(adult acute Lymphoblastic Leukemia, ALL)中IL7R突變與IL7R的表達(dá)特征及其臨床意義。方法：本研究通過對(duì)成人ALL患者(144例)IL7R外顯子(exon) 2-8進(jìn)行擴(kuò)增、克隆和測(cè)序,研究IL7R突變的發(fā)生率、突變位點(diǎn)和類型。通過實(shí)時(shí)熒光定量PCR檢測(cè)ALL患者IL 7R mRNA表達(dá)水平。分析IL7R突變及表達(dá)異常與NOTCH1、PHF6突變的相關(guān)性及其預(yù)后意義。統(tǒng)計(jì)學(xué)分析采用SPSS20.0軟件,白細(xì)胞計(jì)數(shù)(white blood cell,WBC)、骨髓(bone marrow,BM)原始細(xì)胞數(shù)、外周血(peripheral blood,PB)原始細(xì)胞數(shù)等計(jì)量資料的差異采用非參數(shù)Mann-Whitney檢驗(yàn)；計(jì)數(shù)資料采用χ2檢驗(yàn)(或Fisher精確檢驗(yàn))進(jìn)行差異性分析；Kalplan-Meier檢驗(yàn)方法分析生存曲線。P0.05認(rèn)為結(jié)果具有統(tǒng)計(jì)學(xué)意義。結(jié)果：本組成人ALL患者中IL7R的突變率為2.8%,均為缺失或插入突變(為外顯子5和6)；本組研究中觀察到5種SNP(Single Nucleotide Polymorphisms)改變,分別位于exon2(rs1494558),exon4(rs1494555、rs2228141)和exon8 (rs3194051、rs2229232);同時(shí),本研究還觀察到IL7R突變與NOTCH1和/或PHF6突變共存。T-ALL患者中IL7R低表達(dá)組的無進(jìn)展生存(progression free survival,PFS)時(shí)間長(zhǎng)于高表達(dá)組(P=0.036)。結(jié)論：T-ALL患者中IL7RmRNA高表達(dá)組PFS更短,IL7R表達(dá)水平在成人T-ALL患者中可能具有預(yù)后價(jià)值。第二部分 JAK3在成人T細(xì)胞性急性淋巴細(xì)胞白血病中的突變研究目的：JAK3是JAKs (Janus Kinase)家族成員之一,在介導(dǎo)細(xì)胞因子受體胞內(nèi)信號(hào)中扮演重要角色。在多種造血系統(tǒng)腫瘤中已發(fā)現(xiàn)JAK3功能異常。本文目的在于研究成人T細(xì)胞性急性淋巴細(xì)胞白血病(T-cell acute lymphoblastic leukemia, T-ALL)中JAK3基因突變。方法：本研究通過對(duì)成人ALL患者JAK3外顯子(exon) 6、11、12、15、19進(jìn)行擴(kuò)增和測(cè)序,研究JAK3突變發(fā)生率,突變位點(diǎn)和類型、與IL7R/JAK突變的相關(guān)性及其預(yù)后意義。統(tǒng)計(jì)學(xué)分析采用SPSS20.0軟件,白細(xì)胞計(jì)數(shù)(white blood cell,WBC).骨髓(bone marrow, BM)原始細(xì)胞數(shù)、外周血(peripheral blood,PB)原始細(xì)胞數(shù)等計(jì)量資料的差異采用非參數(shù)Mann-Whitney檢驗(yàn)；計(jì)數(shù)資料采用χ2檢驗(yàn)(或Fisher精確檢驗(yàn))進(jìn)行差異性分析；Kalplan-Meier檢驗(yàn)方法分析生存曲線。P0.05認(rèn)為結(jié)果具有統(tǒng)計(jì)學(xué)意義。結(jié)果：本研究只在成人T-ALL (39例)發(fā)現(xiàn)JAK3突變,突變率為12.8%(5/39),共發(fā)現(xiàn)3種點(diǎn)突變(M511I,Y886終止,R887H)；同時(shí),本組研究觀察到1例JAK3突變與IL7R突變共存,未發(fā)現(xiàn)與JAK1突變共存；T-ALL患者中IL7RIJAK信號(hào)通路突變組中位年齡大于無突變組(38.4歲vs.27.9歲,P=0.017), IL7RIJAK信號(hào)通路突變組CD8陽性率明顯低于無突變組(273%vs.70.4%,P=0.019)。結(jié)論：IL7R/JAK信號(hào)通路突變?cè)诔扇薚-ALL發(fā)病機(jī)制中有重要作用。
[Abstract]:Part I mutation, expression and Clinical significance of IL-7R in Adult Acute Lymphocytic Leukemia objective: IL-7R is the receptor of IL-7. IL-7R is composed of IL-7Raand 緯 c. The purpose of this study was to investigate the expression of IL-7R mutation and IL-7R in adult acute of adult patients with acute lymphoblastic leukemia (ALLL) and its clinical significance. Methods: in this study, the incidence, mutation site and type of IL-7R mutation were studied by amplification, cloning and sequencing of exon 2-8 from 144 adult all patients. The expression of IL 7 R mRNA in all patients was detected by real time fluorescent quantitative PCR. To analyze the relationship between IL-7R mutation and abnormal expression of IL-7R and NOTCH1 / PHF6 mutation and its prognostic significance. Statistical analysis was performed with SPSS 20.0 software. The difference of the number of white blood cell (WBC) and the number of PBs in peripheral blood were measured by non-parametric Mann-Whitney test. 蠂 2 test (or Fisher accurate test) was used to analyze the difference of the counting data. The survival curve was analyzed by Kalplan-Meier test. The result was statistically significant. Results: the mutation rate of IL 7R in adult all patients was 2.8, which was deletion or insertion mutation (exon 5 and 6). The changes of 5 SNPs single Nucleotide Polymorphismswere observed in exon2rs1494558exon4rs149455rs2228141 and exon8 rs3194051rs2229232, respectively. It was also observed that the time of progressive free survival PFSs in IL-7R and NOTCH1 and / or PHF6 low expression group was longer than that in high expression group. Conclusion the expression of IL-7R in the high expression of IL-7R mRNA in patients with T-ALL may have prognostic value in adult T-ALL patients. Part two the mutation of JAK3 in adult T cell acute lymphoblastic leukemia objective: JAK3 is a member of the Janus Kinase family and plays an important role in mediating intracellular signal of cytokine receptor. Abnormal JAK3 function has been found in various hematopoietic system tumors. The aim of this study was to study the mutation of JAK3 gene in T-cell acute lymphoblastic leukemia, T-ALL of adult T cell acute lymphoblastic leukemia. Methods: in this study, we amplified and sequenced the JAK3 exon 61112A151519 in adult all patients, and studied the incidence, mutation site and type of JAK3 mutation, the relationship between JAK3 mutation and IL-7RJAK mutation and its prognostic significance. SPSS 20.0 software was used to analyze the white blood cell count. The difference of bone marrow (BMN) primordial cells and peripheral blood PBs was measured by non-parametric Mann-Whitney test, and the difference was analyzed by 蠂 2 test (or Fisher accurate test). Kalplan-Meier test analysis of survival curve. P05 that the results were statistically significant. Results: in this study, only 39 adults (T-ALL) found JAK3 mutation with a mutation rate of 12.80.Three point mutations (M511IY886) were found to terminate R887H1.At the same time, one case of JAK3 mutation coexisted with IL7R mutation, but not with JAK1 mutation. In T-ALL patients, the median age of IL-7RIJAK signal pathway mutation group was larger than that of non-mutation group. The CD8 positive rate of IL-7RIJAK signal pathway mutation group was significantly lower than that of non-mutation group. Conclusion the mutation of IL 7 R / JAK signaling pathway may play an important role in the pathogenesis of adult T-ALL.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R733.71

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1 肖麗嬋;成人急性淋巴細(xì)胞白血病預(yù)后分子標(biāo)記IL7R和JAK3特征研究[D];南京醫(yī)科大學(xué);2016年

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本文編號(hào)：2019767