The Application Of DNA Methylationin Acute Myeloid Leukemia And Myelodysplasticsyndrome

Objectives:Research the effect of the AWT1 gene promoter region methylation level on the prognosis of leukemia.Methods:Bisulfite sequencing method(BSP) detection of leukemia cell line(K562),AML bone marrow mononuclear cells,normal bone marrow mononuclear cells AWT1 gene methylation in the promoter region of the state;Results:1.The rate of AWT1 methylation in K562 cell lines:100%;2.The methylation level of AWT1 gene in AML patients with bone marrow: 24 cases of bone marrow in acute myeloid leukemia patients with AWT1 gene promoter region methylation level : 88%、80%、80%、80%、80%、80%、76%、76%、72%、72%、72%、72%、68%、64%、64%、64%、64%、64%、60%、60%、60%、60%、28%、20%,the average methylation rate:(67±15)%.3. The methylation level of AWT1 gene promoter regionin 6 cases of normal human bone marrow::0%、0%、0%、0%、16%、24%, the average methylation rate:(6.7±11)%4.Treatment and survival of patients with AWT1 hypermethylation:To the end of follow-up,14 cases of disease free survival, 8 cases died, 5 cases died of recurrence, 1 casedied of GVHD, 2 cases of transplantation related mortality. 22 cases of patients with a median survival time of 37.5 months to 3 years(0.5-44), OS rate was 68.2%.Conclusions:AWT1 hypermethylation in patients with AML,AWT1 hypomethylation in normal bone marrow.Objectives:To evaluate the efficacy of DAC(decitabine) bridge therapy followed by allo-HSCT(allogeneic hematopoietic stem cell transplantation) in patients with MDS /Relapsed and refractory AML.Methods:A retrospective analysis of decitabine bridge therapy followed by allo-HSCT in 98 patients, from July 2010 to December 2013, the First Affiliated Hospital of Soochow University, Department of Hematology, The diagnosis of MDS patients with a total of 58 cases, which accepted as DAC bridging graft in 25 cases, more than for the untreated DAC bridge for transplantation,who receive other treatments followed by allo-HSCT,;The diagnosis of AML patients with a total of 40 cases, which accepted as DAC bridging graft in 25 cases, more than for the untreated DAC bridge fortransplantation,who receive other treatments followed by allo-HSCT.comparing patients’ m CR rate, OS and GVHD after DAC bridge therapy.Results:MDS:With decitabine bridge therapy,64% patients achieved marrow complete remission,and the control group was 15.1%(64% vs 15.1%)(P<0.05). Decitabine bridging group of early transplant-related mortality than the control group(4% vs 18.2%), but the difference was not statistically significant(P=0.106). To follow-up deadline, decitabine group mortality was 12%, the control group was 30.3%(P=0.122). Decitabine group of 2-year OS was 83%, the control group was 59%(P<0.05). Patients with IPSS intermediate-1 receiving decitabine bridging the OS rate was higher, the difference was statistically significant. GVHD occurred decitabine bridging group was 56% and the control group a GVHD incidence of 48.5%(P=0.713). a GVHD extent decitabine group is less than the control group(P<0.05).Relapsed and refractory AML:Before transplantation, CR rate of DAC bridging group was lower than the control group(CR rate of DAC bridging group is 45%, CR rate of the control group is 65%); The 3 year OS rate of DAC bridging group of was higher than the control group(3 year OS rate of DAC bridging group is 46.1%,3 year OS rate of the control group is 34.1%),the differences were statistically significant.Conclusions:Decitabine bridging therapy followed by allo-HSCT in the treatment of myelodysplastic syndrome/ Relapsed and refractory AML is safe and effective.