本文選題：淋巴瘤 + 外周T細(xì)胞淋巴瘤�。� 參考：《青島大學(xué)》2017年碩士論文

【摘要】：目的探討TET2(ten-eleven-trantranslocation 2)和DNMT3A(DNA Methyltransferase 3A)在外周T細(xì)胞淋巴瘤(peripheral T-cell lymphoma,PTCL)各亞型中的表達(dá)情況及意義,及其與外周T細(xì)胞淋巴瘤免疫分型及臨床病理特征的關(guān)系及意義。方法1.根據(jù)已標(biāo)記的一系列免疫組織化學(xué)標(biāo)記:CD3、CD4、CD10、BCL-6、CXCL-13、CD30、EMA、ALK(缺少標(biāo)記的補(bǔ)做),可將PTCL患者分為血管免疫母細(xì)胞性T細(xì)胞淋巴瘤(angioimmunoblastic T cell lymphoma,AITL)、外周T細(xì)胞淋巴瘤,非特指(peripheral T-cell lymphomas,not otherwides,PTCL-NOS)、間變性淋巴瘤激酶陽性的間變性大細(xì)胞淋巴瘤(anaplastic lymphoma kinase positive anaplastic large cell lymphoma,ALK+ALCL)和間變性淋巴瘤激酶陰性的間變性大細(xì)胞淋巴瘤(anaplastic lymphoma kinase negative anaplastic large cell lymphoma,ALK-ALCL)四種類型。2.應(yīng)用免疫組織化學(xué)方法檢測89例PTCL患者組織中TET2和DNMT3A的表達(dá)情況,分析二者表達(dá)的相關(guān)關(guān)系及與PTCL各亞型及臨床病理特征的關(guān)系。結(jié)果1.89例PTCL病例中,AITL36例,占40.44%,PTCL-NOS26例,占29.21%,ALK-ALCL18例,占20.22%,ALK+ALCL9例,占10.11%。2.TET2和DNMT3A在PTCL病例中均表達(dá)與細(xì)胞質(zhì)及細(xì)胞核。3.TET2和DNMT3A在AITL病例中高表達(dá)率均高于PTCL-NOS(P=0.005,P=0.048)、ALCL(P=0.001,P=0.001),差異均有統(tǒng)計學(xué)意義。4.在細(xì)胞質(zhì)表達(dá)中,TET2細(xì)胞質(zhì)表達(dá)的高表達(dá)率在AITL病例中均高于PTCL-NOS(P=0.001)和ALCL(P0.001),差異均有統(tǒng)計學(xué)意義;DNMT3A細(xì)胞質(zhì)表達(dá)的高表達(dá)率在AITL病例中均高于PTCL-NOS(P=0.029)、ALCL(P=0.024),差異均有統(tǒng)計學(xué)意義。5.在細(xì)胞核表達(dá)中,DNMT3A細(xì)胞核表達(dá)的高表達(dá)率在AITL中均高于PTCL-NOS(P=0.047)、ALCL(P0.001),差異均有統(tǒng)計學(xué)意義。6.在PTCL病例中,TET2表達(dá)和DNMT3A表達(dá)成正相關(guān)關(guān)系(r=0.384,P0.001);TET2細(xì)胞質(zhì)表達(dá)和DNMT3A細(xì)胞質(zhì)表達(dá)成正相關(guān)關(guān)系(r=0.350,P=0.001);TET2細(xì)胞質(zhì)表達(dá)和DNMT3A胞核表達(dá)成正相關(guān)關(guān)系(r=0.365,P0.001)。7.在AITL病例中,TET2表達(dá)和DNMT3A表達(dá)成正相關(guān)關(guān)系(r=0.478,P=0.003);TET2細(xì)胞質(zhì)表達(dá)和DNMT3A細(xì)胞質(zhì)表達(dá)成正相關(guān)關(guān)系(r=0.336,P=0.045);TET2細(xì)胞質(zhì)表達(dá)和DNMT3A細(xì)胞核表達(dá)成正相關(guān)關(guān)系(r=0.478,P=0.003)。8.有B癥狀PTCL患者中TET2細(xì)胞核高表達(dá)率高于無B癥狀患者,差異有統(tǒng)計學(xué)意義(P=0.003);在III+IV期PTCL患者中,TET2細(xì)胞質(zhì)高表達(dá)率高于I+II期PTCL患者,差異雖無統(tǒng)計學(xué)意義,但處于臨界水平(P=0.061)。9.TET2和DNMT3A的表達(dá)與PTCL患者年齡、性別、LDH水平和IPI評分、結(jié)外浸潤無關(guān)。結(jié)論TET2和DNMT3A異�？赡芫鶇⑴c了PTCL的發(fā)病,TET2和DNMT3A失活導(dǎo)致DNA甲基化異常及造血干細(xì)胞增殖和分化異常進(jìn)而可能參與了PTLC的發(fā)生發(fā)展,為PTCL的治療提供了新的研究思路和策略。TET2和DNMT3A可以作為明確診斷AITL的分子標(biāo)志物,為AITL的明確診斷提供了新的策略。
[Abstract]:Objective to investigate the expression and significance of TET2(ten-eleven-trantranslocation _ 2 and DNMT3A(DNA Methyltransferase _ 3A in peripheral T-cell lymphoma of peripheral T cell lymphoma and their relationship with the immunological classification and clinicopathological features of peripheral T cell lymphoma. Method 1. According to a series of labeled immunocytochemical markers: CD10CL-6, CXCL-13, CD30, EMA-ALK, PTCL patients can be divided into angioimmunoblastic T cell lymphoma (PTCL) and peripheral T-cell lymphoma (T-cell lymphoma). There were four types of non-specific T-cell lymphomatosis: PTCL-NOSU, anaplastic lymphoma kinase positive anaplastic large cell lymphoma (ALK ALCLL) and anaplastic large cell lymphoma (ALK-ALCLL) and anaplastic lymphoma kinase negative anaplastic large cell lymphoma (ALK-ALCLL). Immunohistochemical method was used to detect the expression of TET2 and DNMT3A in 89 patients with PTCL. The correlation between the expression of TET2 and DNMT3A and the relationship between the expression of TET2 and PTCL subtypes and clinicopathological features were analyzed. Results 1.AITL was found in 36 cases of PTCL, accounting for 40.444.There were 26 cases of PTCL-NOS, accounting for 29.21 cases of ALK-ALCLL, accounting for 20.222 cases of ALK ALCL9. The expression of 10.11%.2.TET2 and DNMT3A in PTCL cases were both higher than those in AITL cases and the high expression rates of cytoplasm and nucleus .3.TET2 and DNMT3A were higher than those in AITL cases. The high expression rate of cytoplasm in AITL was higher than that in PTCL-NOSP 0.001) and ALCLT P0.001. The difference was statistically significant. The high expression rate of cytoplasm of DNMT3A was higher in AITL than that in PTCL-NOSP 0.029 ALCLP0.0244.The difference was statistically significant. The high expression rate of DNMT3A in nuclear expression was higher in AITL than that in PTCL-NOSP 0.047 and ALCLT P0.001, and the difference was statistically significant. There was a positive correlation between the expression of Tet T 2 and the expression of DNMT3A in patients with PTCL. There was a positive correlation between the expression of Tet T 2 and the expression of DNMT3A in the cytoplasm and the cytoplasm of DNMT3A. There was a positive correlation between the expression of T T 2 and the expression of DNMT3A. There was a positive correlation between the expression of Tet T 2 and the expression of DNMT3A in AITL patients. There was a positive correlation between the expression of Tet T 2 and the expression of DNMT3A cytoplasm. There was a positive correlation between the expression of T T 2 and the expression of DNMT3A nucleus. The high expression rate of TET2 nucleus in patients with PTCL with B symptom was higher than that in patients without B symptoms, the difference was statistically significant, and the high expression rate of cytoplasm in patients with PTCL in stage IV of III was higher than that in patients with PTCL in stage I II, although the difference was not statistically significant. However, the expression of PTET2 and DNMT3A at the critical level was not related to age, sex, IPI score and extranodular invasion. Conclusion the abnormality of TET2 and DNMT3A may be involved in the pathogenesis of PTCL. DNA methylation abnormality and abnormal proliferation and differentiation of hematopoietic stem cells may be involved in the pathogenesis of PTCL and the inactivation of TET2 and DNMT3A, which may be involved in the occurrence and development of PTLC. TET2 and DNMT3A can be used as molecular markers for the diagnosis of AITL and a new strategy for the definite diagnosis of AITL.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R733.1

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