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The Expression And Significance Of P33ING1b In Acute Leukemia

Posted on:2013-08-21Degree:MasterType:Thesis
Country:ChinaCandidate:Y N ZhuFull Text:PDF
GTID:2234330371977018Subject:Department of Hematology
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Background and PurposeAcute Leukemia (Acute Leukemia, AL), it is a serious threat to human health of cancer for it’s increased high morbidity and mortality. The characteristics of AL is the original or childish abnormal cell proliferation, differentiation and apoptosis is inhabited. The pathogenesis of AL is not clear, but research shows that it has contact with protocarcinogenic gene activation and the inactivation of tumor-suppressor gene. Tumor-suppressor gene is a important change factor that leads to cell abnormal.This abnormal function of cells is caused by many reasons such as gene loss, mutation, displacement and so on.It play a negative role in cell growth. Tumor suppressor gene is an initiation factor for malignant cells,which caused by many reasons causing dysfunction such as gene deletion, mutation, dislocation, and has the negative regulation of cell growth. Growth inhibitory factor-1(Inhibitor of growthl, ING1) is a recently discovered tumor suppressor gene, widely expressed in normal human tissues and a variety of tumor tissue, and related to cell cycle regulation, through different transcription cut way to translate the different molecular proteins, P33ING1b is the main product of its transcription and translation as well as important tumor suppressor gene. The phenomenon of its nuclear expression decreased and cytoplasmic over-expression may occur in some benign and almost all malignant tissue cells. ING1gene translate a molecular weight of alien protein by different shear mode and p33ING1b is the protein encoded by ING1,involved in a variety of biological function mechanism such as cell cycle regulation depends on its phosphorylation state, playing a very important role in tumor development. In normal tissue cells, p33ING1b protein reduced from GO to G1phase, increased in the G1late phase and reached its maximum in the S phase, and then lower in the G2phase.In recent years, related studies have shown that P33INGlb protein expressed in the nucleus of bone marrow mononuclear cells in normal human and acute leukemia patient. The possible mechanisms of p33ING1b in the pathogenesis of acute leukemia have been reported, but the detection of p33ING1b by PCR in acute leukemia patients has not been reported in the domestic. This issue through real-time quantitative PCR to found the difference of the INGlb gene expression level between normal human and AL patients with different stages, analysing the relatation between p33ING1b and the clinical relevance of AL patients and exploring its possible mechanism in the AL.Methods1. An object of study:65cases from our hospital or clinic patients with acute leukemia from December2010to March,2012, the average age is34(15-68) years.(1) The untreated group,46cases;20males and26females, including32cases of acute myeloid leukemia (AML)(AML-M219cases,7cases of AML-M3AML-M52cases),14cases of acute lymphoblastic leukemia (ALL);(2) complete remission group,12cases;8cases of AML,4cases of ALL;(3) The group of7cases of recurrence;3males and4females;(4) normal control group;8cases non-hematologic malignancies patients with normal bone marrow.2. RNA extraction and reverse transcription:bone marrow samples, separate mononuclear cells,then extract experiment total cellular RNA by Trizol and detect the quality and concentration,maging under ultraviolet light, and then systematic observation, analysis the experimental results and photographed using gel image analysis. 3. Statistical analysis:Using Software SPSS17.0analyze the data. Quantitative data were expressed as mean±tandard deviation (x±SD); Paired means were analyzed by Independent-Samples t-test, while Various means were analyzed by variance analysis. Qualitative data were analyzed by chi-square test; The standard of significant level was a=0.05.Result1. p33ING1b in the untreated group of AL, the positive rate of45.7%(21/46), recurrent group was42.9%(3/7), the remission group was58.3%(7/12), the expression level of the P33were0.203±0.106,0.389±0.027,0.627±0.202; normal control group, the positive rate was87.5%(7/8). The positive rate of the recurrence group was significantly lower than the positive rate of the remission group and normal control group, the difference between the recurrence group and the latter two groups was statistically significant (p<0.05); the difference of the positive rate between the early treatment group and remission group had no statistically significant (p>0.05) but the difference of expression level was statistically significant (p<0.05); the differences of expression levels and the positive rate between the recurrence group and the remission group were statistically significant (p<0.05);2. the positive expression rate was45.5%(20/44) in AML,52.38%(11/21) in ALL, the expression levels of two sets were0.491±0.173,0.495±0.221, the differences of the positive rate and expression levels had no statistically significant (p>0.05).3. The expression level of p33ING1b mRNA has no significant correlation with the bone marrow and infiltration, patients for gender, age,(p>0.05).Conclusion1. p33ING1b low expressed in the AL; the expression of recurrence is lowest, the difference had statistics meaning, this may indicate lower expression of p33ING1b gene may play a role in the occurrence and development of acute leukemia. 2. p33ING1b has low expression level in the AML group and ALL group group, the difference was statistically significant, suggesting that the low-expression of p33ING1b may had no meaning to the type of acute leukemia.3. The expression level of p33ING1b in acute leukemic patients has no relevation witn gender, age, and infiltration.
Keywords/Search Tags:Inhibitor of growth1, Acute Leukemia, RT-PCR
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