MiR-128、MiR-17、MiR-18a在儿童急性淋巴细胞白血病中的表达及临床意义

发布时间：2018-04-22 18:28

本文选题：儿童 + 急性淋巴细胞性白血病　；参考：《苏州大学》2012年硕士论文

【摘要】：目的：miRNA是长度为18～25个核苷酸的非编码RNA，人体内50%~60%的蛋白编码基因受到miRNA的调控，依靠其复杂的调控网络，在骨髓造血功能和急性白血病形成过程中也担任着重要角色。本研究对miR-128、miR-17、miR-18a在儿童ALL的表达进行研究，研究其在儿童急性淋巴细胞白血病中的表达，了解其是否与ALL诊断分型、判断预后及提示复发有关，探讨其临床意义。方法：急性淋巴细胞性白血病患儿骨髓标本63例，其中初诊患儿标本48例，，缓解10例，复发5例，正常对照患儿标本10例。提取其骨髓或外周血标本总RNA，并进行引物特异性逆转录成cDNA，运用qRT-PCR技术对miR-128、miR-17、miR-18a进行检测，循环阈值(Ct值)比较法进行miRNA表达定量分析。统计分析初诊ALL、缓解及复发患儿间三种miRNA表达是否有差异，并根据临床资料进行进一步分析，以探讨三种miRNA在儿童ALL中的作用。结果：MiR-128、miR-17、miR-18a在儿童ALL初诊及复发患儿显著高表达(P0.05)，而化疗后缓解的患儿其表达量下降，结合临床资料(危险程度、免疫分型、染色体、融合基因、早期治疗反应)做了进一步分析，发现miR-128、miR-17在T-ALL中的表达量高于B-ALL，差异有统计学意义（P值分别为0.002、0.014）；而随着危险程度的升高，miR-128表达量升高，标危、中危、高危三组之间miR-128的表达有显著差异。MiR-17及miR-18a在MLL基因重排阳性患儿中高表达，提示miR-17及miR-18a可能参与MLL基因重排ALL的形成，并影响其预后。结论：MiR-128、miR-17、miR-18a在儿童ALL初诊及复发患儿高表达，且随着危险度的增高，MiR-128的表达增高；说明其表达可能与儿童ALL的发病及危险度相关，对ALL的诊断及复发的判断有一定的指导意义，提示是否可以作为ALL诊断及监测化疗效果的分子标记。MiR-128及miR-17在T-ALL高表达，提示他们是否可作为区分B系及T系不同免疫分析的指标；miR-17及miR-18a在MLL基因重排阳性患儿中高表达，提示miR-17及miR-18a可能参与MLL基因重排ALL的形成，两者是否可以作为判断高危ALL的分子标记。
[Abstract]:Objective: miRNA is a non-coding RNAs with a length of 18 ~ 25 nucleotides. Fifty percent of the protein coding genes in human body are regulated by miRNA. Depending on its complex regulatory network, it also plays an important role in bone marrow hematopoiesis and acute leukemia formation. In this study, we studied the expression of miR-128miR-17miR-18a in children with acute lymphoblastic leukemia (ALL), and investigated whether the expression of miR-128miR-17miR-18a in children with acute lymphoblastic leukemia was related to the diagnosis and classification of ALL, the prognosis and recurrence, and to explore its clinical significance. Methods: the bone marrow specimens of 63 children with acute lymphoblastic leukemia were collected, including 48 cases of newly diagnosed children, 10 cases of remission, 5 cases of recurrence and 10 cases of normal controls. The total RNAs of bone marrow or peripheral blood samples were extracted, and the specific reverse transcription of primers was carried out into cDNA.MiR-128 miR-17 miR-18a was detected by qRT-PCR technique, and the miRNA expression was quantitatively analyzed by cyclic threshold value (Ct) comparison method. The expression of three kinds of miRNA in newly diagnosed children with ALL, remission and recurrence was statistically analyzed, and further analysis was made according to the clinical data to explore the role of three kinds of miRNA in children with ALL. Results the proportion of miR-128miR-17miR-18a was significantly higher in children with ALL at first diagnosis and recurrence, but the expression of P0.05a was decreased in children with remission after chemotherapy. Further analysis was made in combination with clinical data (risk degree, immune typing, chromosome, fusion gene, early treatment response). It was found that the expression of miR-128 miR-17 in T-ALL was higher than that in B-ALL, and the difference was statistically significant (P = 0.002) 0.014, while the expression of miR-128 increased with the increase of risk, and the expression of miR-128 in T-ALL was higher than that in B-ALL, and the expression of miR-128 in T-ALL was higher than that in B-ALL. There was significant difference in the expression of miR-128 between the three groups. MiR-17 and miR-18a were highly expressed in MLL gene rearrangement positive children, suggesting that miR-17 and miR-18a might be involved in the formation of MLL gene rearrangement ALL and affect its prognosis. ConclusionMiR-128 miR-17miR-18a is highly expressed in children with ALL at first diagnosis and recurrence, and the expression of MiR-128 is increased with the increase of risk, which indicates that the expression of miR-18a may be related to the pathogenesis and risk of ALL in children, and has certain guiding significance in the diagnosis and recurrence of ALL. It is suggested that they can be used as molecular markers for the diagnosis and monitoring of chemotherapeutic effect of ALL. MiR-128 and miR-17 are highly expressed in T-ALL. It is suggested that they can be used as markers for differentiating different immunological analysis of B and T lines, and whether they can be used as markers for high expression of MLL gene rearrangement in children with positive MLL gene rearrangement. It is suggested that miR-17 and miR-18a may be involved in the formation of MLL gene rearrangement ALL, and whether they can be used as molecular markers to judge high risk ALL.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R733.7

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