| Objective： Acute myeloid leukemia (AML) is a tumor of highlymalignant cloning proliferation. In recent years, with the popularity ofmolecular biology techniques, the number of gene mutations and abnormalgene expression (including FLT3mutations, NPM1and CEBPA) were foundin patients with normal karyotype acute myeloid leukemia (CN-AML)., andsignificantly affect the clinical outcome. The discovery and study of molecularmarkers provides an important basis for the CN-AML diagnosis, treatment andprognosis.The biological functions of GATA2in hematopoietis and the importanceof its balanced expression led to the suggestion that it might be involved inleukemogenesis. Since GATA2levels decreased with differentiation in each ofthe various hematopoietic sub-lineages, this pattern might reflect the ability ofoverexpressed or activated GATA2to suppress normal differentiation andpromote leukemic transformation. CREB-binding proteins (CBP) as atranscriptional coactivator of GATA-2。CBP is a transcription adaptor by directbridging between basic transcription factors and several sequence-specifictranscriptional activator. Both in vivo or in vitro CBP can combination withGATA-2, and be able to improve the activity of GATA-2transcriptionalactivation in a dose-dependent manner. CBP protein expression of GATA-2selective binding to maintain the undifferentiated state of hematopoietic cells,it is this state of hematopoietic progenitor cells and development mechanismwill help us to control the leukemia and abnormal differentiation ofhematopoietic progenitor cells diseases. The study was to investigate therelationship between the expression of GATA-2/CBP and the development ofacute leukemia, then to investigate whether there was some relationship between the coexpression of GATA-2/CBP and the pathogenesis of acuteleukemia. Multi-angle and other aspects of cell development, proliferation,differentiation-depth study of the expression characteristics of the GATA-2and CBP in the development of acute leukemia, which gradually clear itsmechanism, to provide new ideas for the treatment of CN-AML and toimprove the cure of leukemiarate and long-term disease-free survival lay thefoundation。Methods:1Collect bone marrow fluid samples of2011.4-2012.1part inthe Second Hospital of Hebei Medical University, inpatient and outpatient fora total of87cases of AML patients(including34cases of untreated CN-AMLpatients,45cases of complete remission patients,8cases of relapse CN-AMLpatients), and11cases of normal group (patients with non-hematologicmalignancies).2Using the lymphocyte separation medium separation of bone marrowmononuclear cells;3Semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR)to detect GATA2and CBP mRNA levels of each group;4StatisticallyResults:1The expression level of GATA2mRNA in each group1.1The expression of GATA2mRNA in de novo CN-AML patients(mean1.299(1.469),positive rate97.1%) and in relapse (RP) CN-AMLpatients (mean1.367(1.734),positive rate100%). There was no differencebetween de novo and RP group。But de novo group were significantly higherthan NC (mean0.592(0.916), positive rate54.5%)(P <0.05). The expressionof GATA2mRNA in CR group (mean0.412(1.079), positive rate88.9%)were lower than that in de novo CN-AML patients (P<0.05). But there was nodifference between CR group and NC group(P>0.05)。1.2The de novo CN-AML patients were divided into GATA2highexpression group and GATA2low expression group. The CR rate was92.31%in GATA2high expression group, The CR rate was75%in GATA2lowexpression group, there was no difference between the GATA2high expression group and GATA2low expression group (P>0.05).2The expression level of CBP mRNA in each group2.1The mean expression of CBP mRNA in de novo CN-AML patientswas1.070(1.661), the positive rate was97.1%(33/34). In the RP-patients,the mean expression was1.546(0.347), the positive rate was100%(8/8). Inthe CR-patients, the mean expression was0.451(0.908), the positive rate was93.3%(42/45). In the NC group, they were0.591(0.358) and100%(11/11)separately. In addition to the de novo group and the RP group, the CR groupand the NC group, CBP mRNA expression level in the rest of each group inthe AL have significantly difference.2.2The de novo CN-AML patients were divided into CBP highexpression group and CBP low expression group. The CR rate was83.33%inCBP high expression group, and there was no difference between the CBPhigh expression group and the CBP low expression group (CR rate80.95%)(P>0.05).3There were94.12%de novo CN-AML patients measured to expressboth GATA2and CBP mRNA.4There was no correlated between GATA2, CBP expression level andthe white blood cell count, hemoglobin, platelet count and the original numberof immature cells in the de novo group (P>0.05). Detected18CN-AMLpatients, GATA2and CBP mRNA expression level and CD34+cell countWere related to analysis, we find that there is no significant correlation (P>0.05)。5The expression level of GATA2and CBP in the de novo group andCR groupTracking observation the16patients with CN-AML, detected theGATA2and CBP expression level of bone marrow mononuclear cells inthe de novo group and CR group. The results showed that GATA2expressionlevels in the de novo group is1.699(1.243), Significantly lower than the denovo group, the difference was statistically significant (P <0.05). CBPexpression levels in the de novo group is1.437(2.160), To ease after the CBP expression level is0.323(0.919),was significantly lower than beforetreatment, the difference was statistically significant (P <0.05)。Conclusions:1In de novo and relapsed CN-AML patients, the expression of GATA2mRNA abnormally increases; however,the expression is lower in completeremission group, there is no difference compared with normal group. Theexpression of CBP mRNA in de novo and relapsed patients are higher than inthe normal group and remission patients, the difference between the groupsare statistically significant. In summary, GATA2and CBP may play a moreimportant role, and provide a theoretical basis for the AML stratifiedtreatment.2The expression level of GATA2and CBP does not affect the CRrate.Compared with the expression before chemotherapy, the expression oftwo genes obviously decrease after complete remission. Dynamic monitoringGATA2and CBP mRNA can be used as indicators to evaluate the therapeuticeffect and predict recurrence.3The expression level of GATA2and CBP mRNA in de novo CN-AMLpatients is correlation. At present, we can assume that GATA2and CBPjointly play a role in the pathogenesis of leukemia. CBP,as a new molecularmarker used in acute leukemia, can be joint GATA2to predict the prognosisof CN-AML. |
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