本文選題：兒童 + 急性淋巴細(xì)胞性白血病　； 參考：《蘇州大學(xué)》2012年碩士論文

【摘要】：目的：miRNA是長(zhǎng)度為18～25個(gè)核苷酸的非編碼RNA，人體內(nèi)50%~60%的蛋白編碼基因受到miRNA的調(diào)控，依靠其復(fù)雜的調(diào)控網(wǎng)絡(luò)，在骨髓造血功能和急性白血病形成過(guò)程中也擔(dān)任著重要角色。本研究對(duì)miR-128、miR-17、miR-18a在兒童ALL的表達(dá)進(jìn)行研究，研究其在兒童急性淋巴細(xì)胞白血病中的表達(dá)，了解其是否與ALL診斷分型、判斷預(yù)后及提示復(fù)發(fā)有關(guān)，探討其臨床意義。 方法：急性淋巴細(xì)胞性白血病患兒骨髓標(biāo)本63例，其中初診患兒標(biāo)本48例，，緩解10例，復(fù)發(fā)5例，正常對(duì)照患兒標(biāo)本10例。提取其骨髓或外周血標(biāo)本總RNA，并進(jìn)行引物特異性逆轉(zhuǎn)錄成cDNA，運(yùn)用qRT-PCR技術(shù)對(duì)miR-128、miR-17、miR-18a進(jìn)行檢測(cè)，循環(huán)閾值(Ct值)比較法進(jìn)行miRNA表達(dá)定量分析。統(tǒng)計(jì)分析初診ALL、緩解及復(fù)發(fā)患兒間三種miRNA表達(dá)是否有差異，并根據(jù)臨床資料進(jìn)行進(jìn)一步分析，以探討三種miRNA在兒童ALL中的作用。 結(jié)果：MiR-128、miR-17、miR-18a在兒童ALL初診及復(fù)發(fā)患兒顯著高表達(dá)(P0.05)，而化療后緩解的患兒其表達(dá)量下降，結(jié)合臨床資料(危險(xiǎn)程度、免疫分型、染色體、融合基因、早期治療反應(yīng))做了進(jìn)一步分析，發(fā)現(xiàn)miR-128、miR-17在T-ALL中的表達(dá)量高于B-ALL，差異有統(tǒng)計(jì)學(xué)意義（P值分別為0.002、0.014）；而隨著危險(xiǎn)程度的升高，miR-128表達(dá)量升高，標(biāo)危、中危、高危三組之間miR-128的表達(dá)有顯著差異。MiR-17及miR-18a在MLL基因重排陽(yáng)性患兒中高表達(dá)，提示miR-17及miR-18a可能參與MLL基因重排ALL的形成，并影響其預(yù)后。 結(jié)論：MiR-128、miR-17、miR-18a在兒童ALL初診及復(fù)發(fā)患兒高表達(dá)，且隨著危險(xiǎn)度的增高，MiR-128的表達(dá)增高；說(shuō)明其表達(dá)可能與兒童ALL的發(fā)病及危險(xiǎn)度相關(guān)，對(duì)ALL的診斷及復(fù)發(fā)的判斷有一定的指導(dǎo)意義，提示是否可以作為ALL診斷及監(jiān)測(cè)化療效果的分子標(biāo)記。MiR-128及miR-17在T-ALL高表達(dá)，提示他們是否可作為區(qū)分B系及T系不同免疫分析的指標(biāo)；miR-17及miR-18a在MLL基因重排陽(yáng)性患兒中高表達(dá)，提示miR-17及miR-18a可能參與MLL基因重排ALL的形成，兩者是否可以作為判斷高危ALL的分子標(biāo)記。
[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.
【學(xué)位授予單位】：蘇州大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2012
【分類(lèi)號(hào)】：R733.7

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