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The Clinical And Experiment Studies On The Expression Of The Antiapoptosis Gene Survivin In Acute Promyelocytic Leukemia

Posted on:2005-03-17Degree:DoctorType:Dissertation
Country:ChinaCandidate:J XueFull Text:PDF
GTID:1104360122472270Subject:Internal Medicine
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The clinical and experiment studies on theexpression of the antiapoptosis gene survivinin acute promyelocytic leukemiaAcute promyelocytic leukemia(APL) is a special type of leukemia. It has unique molecular biological characteristic, i.e.,t(15;17) chromosomaltranslocation and PML/RARa fusion gene. Ninety percent of patients could beeffectively treated with ATRA and As2O3. Up to now very little is known about its cell biology . Recently a newly identified inhibitor of apoptosis, survivin, was found to be expressed in fetal tissue and in many cancers but not in normal adult tissues. Recent researches showed that survivin gene is a antiapoptosis gene. Its presence was related with more aggressive forms of neuroblastoma, and poor survival among patients with colorectal cancer, non-small cell lung cancer, breast cancer, and esophageal cancer. Therefore, survivin gene expression may be associated with unfavourable clinical outcome in cancers. Survivin gene expression is a frequent event in acute leukemia, but is not known in acute promyelocytic leukemia. To our knowledge, the relationship between survivin gene expression and acute promylocytic leukemia has not yet been studied. Here, we investigated the expression of survivin in hematological tumour cell strainsand in acute promyelocytic leukemia and explored its mechanism of regulation. Our experiment is divided into three sections. In the first section, survivin expression was first detected in hematological tumour cell strains. In the second section, survivin expression was analysised in acute promyelocytic leukemia patients. In the third section, we investigated the mechanism of regulation of survivin gene on ATRA, G-CSF, GM-CSF, PHA and survivin AS-ODN.In the first section we investigate the expression profile of survivin gene in hematological tumour cell strains. The transcriptional levels of survivin gene were detected by using RT-PCR. It was found that survivin gene was expressed in 11 hematological tumour cell strains (k562, HL-60, U937, HEL, 6T-CEM, NB4, Jurkat, Raji, MUTZ-1, Dami and k562/ADR cell strain). In addition, our data showed that there existed differential expression of survivin gene in hematological tumour cell strains (NB4 > MUTZ-1 > K562 > Raji > HL-60 > 6T-CEM > U937 > HEL > Jurkat > Dami).The transcriptional levels of survivin gene in k562/ADM cell strain increased 1.6-fold compared with k562 cell strain, but wasn't detected in peripheral blood mononuclear cells(PBMNCs).In the second section we detected survivin gene expression in 36 cases of de novo and relapse and 22 cases of remission period of acute promyelocytic leukemia(APL), 23 cases of acute leukemia and 48 cases of chronic myelocyticleukemia(CML). PML/RAR and survivin mRNA expression were analysed byusing reverse transcriptase polymerase chain reaction(RT-PCR)technique. The experiment result showed as following:1.The positive and negative rate of survivin mRNA expression was 67% and 33%, respectively, in all 36 cases of de novo and relapse APL patients whosePML/RARa fusion gene expression was positive. There are also 22 cases ofremission stage patients whose PML/RAR a fiision gene expression was negative , and the positive and negative rate of survivin mRNA expression was 36% and 64%, respectively. The survivin mRNA expression positive rate in the de novoand relapse groups, and PML/RARa fusion gene L-type positive groups wasobviously higher than in remission period groups(P<0.05) and was obviously lower than in acute leukemia grougs (P<0.05,<0.001).2. Whether the survivin mRNA expression was positive or negative in 36 cases of de novo and relapse APL patients, all of 36 cases could obtain complete remission. 4 APL patients whose the survivin mRNA expression was positive had DIG and serious infection(one patient died). The clinical symptom had slight skin or mucosa bleeding, fever and asthenic for patients whose the survivin mRNA expression was negative. After 2 APL patients whose the survivin mRNA expression was po...
Keywords/Search Tags:Cell strains, NB4, survivin gene, PML/RAR ? fusion gene, acute promyelocytic leukemia, acute leukemia, chronic mylocytic leukemia
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