Role Of Autophagy Related Gene UVRAG In The Malignant Progression Of MDS

Objective:Myelodysplastic syndromes(MDS) is a heterogeneous clonal disorder of hematopoietic stem cells derived from bone marrow. These patients showed a decrease in bone marrow cell morphology, one or more of the blood cells, and the risk of a high risk of acute myeloid leukemia. To investigate the expression of autophagy related gene UVRAG in non malignant hematological diseases(NM), MDS and De novo AML, to explore the relationship between UVRAG expression and disease type, molecular genetic and prognosis in De and novo AML and MDS and role of autophagy related gene UVRAG in the malignant progression of MDS. Methods:1) Using rRT-PCR method for the detection of different leukemia cell lines and 144 cases of blood disease patients of autophagy related gene LC3 B UVRAG mRNA expression and clinical data analysis, including 54 cases of MDS patients, 76 cases of de novo AML patients, patients with nm in 14 cases.2) To observe the number of internal cells of the mononuclear cells of bone marrow mononuclear cells in patients with hematological diseases by transmission electron microscopy. Results:q RT-PCR detection UVRAG and LC3 B mRNA expression was found in different leukemia cell lines, the expression of UVRAG and LC3 B are different. In clinical specimens, expression of LC3 B and UVRAG in malignant hematologic diseasewas significantly lower than that in non malignant hematological diseases(P < 0.05); Expression levels of UVRAG are related with disease degree of malignancy, MDS patients of UVRAG expression was higher than that of de novo AML patients. In MDS patients, the expression of UVRAG was not related to sex, age, HB and PLT counts, and was associated with abnormal cytogenetic and WPSS prognosis, with MDS from low risk to high risk, expression of UVRAG decreased gradually. Transmission electron microscopy confirmed that the level of autophagy of MDS and AML decreased with the increas ing degree of malignant disease. Conclusion:1. The level of autophagy of NM, MDS and AML is negatively correlated with the degree of disease.2. With the MDS from low risk to high risk, the expression of UVRAG was gradually reduced, and MDS malignant progression was negatively correlated.3. UVRAG may be a potential tumor suppressor gene in malignant hematological disease, which may inhibit the malignant progression of MDS and the progression of AML.