The Expression Of COX-2,Bcl-2 And Bax And Their Clinical Application In Leukemia Patents

Objective: Cyclooxygenase(COX)is the key enzyme in the conversion of eicosanoids to PGs. Two isoforms of COX have been identified,namely COX-1 and COX-2. COX-1 is the constitutive gene and regulates normal activity of human body,such as stomatch mucosa protection and platelet agglutination; whereas COX-2 is inducible gene. Cytokines,growth factors,oncogenes,stress stimulating and mitogen have been found to induce COX-2 up-expression. Studies in recent years have founded that COX-2 played a key role in tumorigenesis and development. PGE,a major COX-2 derived product,has been reported to stimulate the tumor cell growth and inhibit cell apoptosis. Seldom reports documented the relationship between COX-2 and leukemia. In order to investigate the relationship between COX-2 and leukemia , our study examined the expression of COX-2,Bcl-2 and Bax in bone marrow cells of untreated acute leukemia,complete remission (CR) stage of leukemia and normal control(NC). At the same time,we tried to find out a relationship between the prognostic significance of acute leukemia and the expression level of COX-2,Bcl-2 and Bax. Materials and method⑴Subjects were divided into three groups:①The untreated Leukemia group(n=20,Male 10,Female 10,Mean age 37.5Y),including acute lymphocytic leukemia (ALL) 5 cases and acute myelogenous leukemia (AML) 15 cases,According to the diagnostic standard worked out by FAB in 1985,AML were further subdivided into M2 3 cases,M3 5 cases,M4 2 cases,and M5 5cases.②The complete remission stage of Leukemia group(n=20,Male 10,Female 10,Mean age 37.5Y),including ALL 5 cases and AML 15 cases. According to the diagnostic standard worked out Suzhou meeting in 1987,AML were further subdivided into M2 3 cases,M3 5 cases,M4 2 cases,and M5 5cases.③The normal control group(n=20,Male 11,Female 9,Mean age 35.5Y).⑵Collecting the mononuclear cells of bone marrow of all Leukemia group and peripheral blood of the normal control group,test the positive rate of COX-2,Bcl-2 and Bax by using RT-PCR method.⑶The results were analyzed with chi-square test by SPSS10.0,and we established the standard of statistic significance as a =0.05.Results1 The average expression level of COX-2 in these three groups are:1.19士0.20,0.75士0.18,0.72士0.17. The average expression level of COX-2 in patients with newly diagnosed untreated Leukemia is significantly higher than that complete remission stage of Leukemia and the normal control group(P<0.05).There is no significant difference between the complete remission group and the normal control group(P>0.05).2 The average expression level of COX-2 in ALL and AML are:The average expression level of COX-2 in newly diagnosed untreated ALL and complete remission stage of ALL are:1.21士0.17,0.77士0.15;The average expression level of COX-2 in newly diagnosed untreated AML and complete remission stage of AML are:1.18士0.14,0.79士0.16.There is no significant difference between the newly diagnosed untreated ALL and the newly diagnosed untreated AML (P>0.05). There is no significant difference between the complete remission stage of ALL and the complete remission stage of AML (P>0.05).3 The average expression level of COX-2 in type M3 and other type of AML are:The average expression level of COX-2 in newly diagnosed untreated type M3 and complete remission stage of M3 are:1.20士0.16,0.74士0.17;The average expression level of COX-2 in newly diagnosed untreated other type of AML and complete remission stage of other type of AML are:1.21士0.19,0.76士0.14. There is no significant difference between the newly diagnosed untreated type M3 and the newly diagnosed untreated other type of AML (P>0.05). There is no significant difference between the complete remission stage of type M3 and the complete remission stage of other type of AML (P>0.05).4 The average expression level of Bcl-2 in these three groups are:1.21士0.18,0.79士0.15,0.75士0.12. The average expression level of Bcl-2 in patients with newly diagnosed untreated Leukemia is significantly higher than that complete remission stage of Leukemia and the normal control group(P<0.05).There is no significant difference between the complete remission group and the normal control group(P>0.05).5 The average expression level of Bax in these three groups are:1.11士0.10,0.91士0.12,0.89士0.14. The average expression level of Bax in patients with newly diagnosed untreated Leukemia is higher than that complete remission stage of Leukemia and the normal control group,but there is no significant difference(P>0.05);There is no significant difference between the complete remission group and the normal control group(P>0.05).6 There is positive correlation between COX-2 and Bcl-2 in three groups;there is no correlation between COX-2 and Bax expressions;there is positive correlation between Bcl-2 and Bax expressions.Conclusion1 COX-2,Bcl-2 and Bax mRNA overexpress in untreated leukemia group. The over expression maybe contribute to the occurrence of leukemia.2 In complete remission,the expression level of COX-2,Bcl-2 and Bax mRNA was lower than untreated leukemia. There are different levels of the expression of COX-2,Bcl-2 and Bax mRNA in different stages of leukemia,we can regard them as monitoring index for the development of leukemia.3 There is positive correlation between COX-2 and Bcl-2 in three groups,there is no correlation between COX-2 and Bax expressions,COX-2 can unregulate the expression of Bcl-2 and COX-2 may play an important role during the proliferation and the malignant transformation of leukemic cells.