| Chronic myeloid leukemia(CML) is one of the most dangerous diseases,its incidence is 0.36 among 100,000 persons in our country every year,accounts for thirdly in acute chronic leukemia. The molecular mechanism of CML is the existence of bcr/abl fusion gene,this gene can be transcripted into 8.5Kb mRNA and translated into 210KDa BCR/ABL fusion protein which has abnormal high activity of tyrosine kinase,abnormally transform the hematopoietic stem cells and result in CML. CML can be clinically divided into chronic,accelerated and blastic phase. The average natural course of disease is 31 months,hi recent decades,the survival period of CML patients was elongated thanks for application of allogeneic hematopoietic stem cells transplantation(allo-SCT),Interferon- a (INF- a ) and unite chemotherapy. But acute leukemia transferred from CML took place in 50-60% patients without allo-SCT among 5 years. So the mechanism of this change is the focus of researcher in our country and abroad at all times. CML transferring is a multi-gene and multi-path process. The conventional research only focused on several genes,leaded to unilateral conclusion,which limited the research progress of CML transferring mechanism. Now we can inspect object genes in high flow-out with the birth of DNA microarray technology,to find out the relationship of genotype and presence completely and systematically. The genes expression difference of bone marrow mono-nuclear cells was examined with gene chip technology in CML chronic and blastic phases. Fifty-one genes(12 transcription genes,11 regulate proteins,8 cell surface antigens,5 metabolism genes,15 others) were up-regulated among 1176 objective genes. Genes up-regulated ten times amount to 18. It was reported that expression of Evi-1 elevated in CML blastic phase. We also found this phemomenon. Evi-1 may be involved in acute leukemia transferred from CML.G proteins were the other genes associated with transferring,as we found 11 G protein genes were up-regulated obviously in our experiment. And some papers reported that the transfer and invasion of tumour cells boost up if the a,2 subunit of G protein genes were up-regulated. It was also found that 17 genes only expressed in blastic phaseof CML. Although the different expression of many genes were found out in our experiment,the relationship of the majority of these genes and leukamia were not clear yet. The results of our experiment can do favor for the future research. INF- a is one of the principal medications for CML therapy. It can not only ease the clinical symptom of CML,but can also achieve a complete cytogeneticresponse(CGCR).The therapeutic mechanism of IFN- a is unknown. Several researches demonstrated that many genes may be involved in this mechanism,such as:oncogenes and tumor suppressors,apoptosis associated genes et al. The change of gene expression profile in K562 cells was studied before and post treatment by IFN- a . No gene expression difference more than 3 times in K562 cells was found on the first day after treatment by IFN- a (200u/ml),then increase step by step,and reach the peak on the forth day,began to decrease on the fifth day. There were still 9 genes which had expression difference more than 3 times on the twenty-first day. So the forth day was considered the best time to detect the effect of IFN- a . 86.60%(84/97) objective genes were up-regulated,13.4%(13/97) were down-regulated at this time. Celll regulator protein genes accounted to 23.71%(23/97),receptor genes accounted to 14.43%(14/97),oncogenes and tumor suppressors accounted to 11.34%(ll/97),cell signaling,extracellular communication proteins accounted to 9.28%(9/97),cell adhesion molecular genes accounted to 8.25%(8/97),the other genes accounted to 32.99%(32/97). JAK1 was up-regulate to 3.7806 times,JAK2 to 15.4321,STAT1 and STAT2 were up-regulated to 11.9766 and 8.107 times respectively,these genes are components of JAK-STAT pathway. It was also discovered that STAT-induced STAT inhibitor 2 to up-regulated to 3.7929 times,this may be a contrary reg... |
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