自噬相关基因UVRAG在MDS恶性进展的作用研究

发布时间：2019-04-03 15:02

【摘要】：目的:骨髓增生异常综合征(Myelodysplastic syndromes,MDS)是起源于骨髓造血干细胞的异质性克隆性疾病。这类病人表现为骨髓细胞形态异常,一系或多系细胞减少,并且具有高危演变为急性髓系白血病的风险。自噬相关基因UVRAG参与细胞的自噬过程,但在血液病中的研究甚少,本实验拟研究自噬相关基因UVRAG在非恶性血液病(NM)、MDS、De novo AML的表达情况,探讨在MDS、De novo AML中UVRAG的表达与疾病类型、分子遗传学和预后的关系,研究自噬相关基因UVRAG在MDS恶性进展中的作用。方法:1)采用qRT-PCR方法检测不同白血病细胞株及144例血液病患者的自噬相关基因LC3B、UVRAG mRNA表达量及临床资料的分析,其中MDS患者54例,De novo AML患者76例,NM患者14例。2)采用透射电子显微镜方法观察血液病患者骨髓单个核细胞胞内自噬体数量情况。结果:q RT-PCR技术检测LC3B、UVRAG mRNA表达发现,在不同白血病细胞株间,LC3B、UVRAG mRNA表达量存在差异;在临床标本中,LC3B、UVRAG mRNA在恶性血液病中的表达明显低于非恶性血液病,其差异有统计学意义(P0.05);UVRAG表达水平与疾病恶性程度有关,MDS患者的UVRAG表达高于De novo AML患者;在MDS患者中,其表达与细胞遗传学异常、WPSS评分有关,随着MDS由低危转向高危,UVRAG表达逐渐降低;透射电子显微镜证实,MDS、AML的自噬水平随着疾病恶性程度增高而降低。结论:1、NM、MDS、AML的自噬水平与疾病恶性程度呈负相关。2、随着MDS由低危转向高危,UVRAG表达逐渐降低,与MDS恶性进展负相关。3、UVRAG可能是恶性血液病中潜在的抑癌基因,抑制MDS恶性进展并向AML转化。
[Abstract]:Objective: Myelodysplastic syndrome (MDS) is a heterogeneous clonal disease derived from bone marrow hematopoietic stem cells. This type of patient appears to be an abnormal form of bone marrow cells, a reduction in one or more lines, and a risk of high-risk evolution to acute myeloid leukemia. The autophagy-related gene, UVRAG, was involved in the autophagy of the cells, but the study of the self-autophagy-related gene UVRAG in the non-malignant hemopathy (NM), MDS, and De novo AML was studied. The expression of UVRAG in MDS, De novo AML and the type of disease were discussed. To study the relationship between molecular genetics and prognosis, and to study the role of autophagy-related gene UVRAG in the progression of MDS. Methods:1) The expression of autophagy-related gene LC3B, UVRAG mRNA and clinical data of 144 patients with various leukemia cell lines and 144 hemopathy patients were detected by the qRT-PCR method, including 54 cases of MDS,76 cases of De novo AML, The number of self-phagocytosis of bone marrow mononuclear cells in patients with hemopathy was observed by means of transmission electron microscopy (TEM). Results: The expression of LC3B and UVRAG mRNA was detected by q-RT-PCR. The expression of LC3B and UVRAG mRNA in different leukemia cell lines was significantly lower than that of non-malignant hemopathy. The level of UVRAG expression is related to the degree of malignancy of the disease, and the UVRAG expression in the MDS patients is higher than that of the De novo AML; in the MDS patients, the expression is related to the cytogenetic abnormality, the WPSS score, and as the MDS is at high risk from low risk to high risk, the expression of the UVRAG is gradually reduced; and the transmission electron microscope confirms that the MDS, The level of autophagy in AML decreases with the severity of the disease. Conclusion: The level of autophagy of 1, NM, MDS and AML is negatively correlated with the degree of malignancy.
【学位授予单位】：苏州大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R551.3

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