Study On Methylation Of The FANCF In Acute Myeloid Leukaemia And Myelodysplastic Syndrome

PrefaceChemotherapy is main therapy of acute medullary leukaemia(AML).But because of drug fast phenomenon and side effect of drug,theresult of therapy on AML is unsatisfied,it is emergencily requested to slove the problem of effective therapy on refractoriness and recuring AML. myelodysplastic syndrome(MDS)is heterogeneity,clone and malignant affectio n.The characteristic of MDS is high risk of transforming to acute leukaemia.A t present,there is no satisfied therapymethod.Methylation of DNA is different from mutation and absence,it dosen't alter ate the DNA sequence.Therefore,methylation of DNA is areversible change,w hich is manipulateable.It is going to be a new therapy method.Methylation of DNA means plus a methylium to 5- carbon atom of cytosine on CpG dinucleoti de,which form 5-methyley-tosine(5mc).methylated DNA contributes to gene mutation,regulationof gene expression and genomic stability,thus it has closely correlateion with cancer.recent investigation discovers that methylation of DN A is ubiquitous phenomenon in leukemia.FA protein group reside in normal bodies,so far,it has been proved to ha ve 11 complementary bloc and 8 FA related gene.A,C,E,F,G protein of FA has effect respectively,composed of nucleoprotein complex and may be dir ectly involved in DNA repair and its own destruction of cell generation cycle d etection signal pathway.FANCF play an important role in FA group,the promot er methylation of FANCF may subsequent disruption of the FA/BRCA pathway. Disrupting the integrity of the FA/BRCA pathway will induce cell to transform into tumor cells,Some investigations testify that the methylation of FANCF co ntributes to ovarian cancer,oral cancer,lung cancer andcervical cancer.But the study on AML and MDS is rare.The purposeof this study is to study the relati onship between methylation status of FANCF and invasion,as well as prognosis of AML and MDS.Hope to find a new target for therapy.Materials and methodThe study object:58 AML patients,(38 first visit,20 comple-te remission) meso-age is 54,M-F is 1.2:1;18 MDS patients,low-danger group has 8 specimens(RA 5,RAS 4),high-danger group has 10 specimens(RAEB 7,RAEB-T 4),meso-age is 69,M-F is 1:1;control group has 20 patients.Whom are megaloblastic anemia,renal anemia,hypoferric anemia,renal anemia and thrombocytolytic purpura.Method:mono-nucleus cell are extracted from bone marrow by FIcoll dens ity gradient centrifugation.then extract DNA from cells.Sulfurize modify the DNA.the methylation special PCR(MS-PCR)w-as used to detect the methylat ion of FANCF.statistical analysis the results by Kruskal-Wallis test of non-par ametric test with SPSS13.0.Resultshyper-methylation was found in group of patients with AML,the-re was sta tistical significance between AML group and control group(p＜0.01).in AML gro up,patients of first visit show higher methylatio-n of FANCF than patients of c omplete remission(CR).There was st-atistical significance in group comparison (p＜0.05).There is no visible different between CR group and control group.Co mparing CR gro-up with control group has no statistically significant(p＞0.05).b oth high-danger and low- danger MDS show high-methylation of FANCF.There was statistical significance between MDS group with control group(P＜0.0 1),as well as between high-danger MDS and low-danger MDS(P＜0.05).ConclutionFANCF in patients with AML and MDS showed hyper-methylated,as well as methylation of FANCF is obviously higher in first visit group than CR group,which hints it probably plays a role in the pathogenesis of AML and MDS.Methylation of FANCF is obviously higher in high-danger MDS than low-danger MDS hints It may be concerned with prognosis of MDS.Remove methylation of FANCF probably become a new target of treatment to AML and MDS. ConclutionFANCF in patients with AML and MDS showed hyper-methylated,the degree of methylation correlated with extent of relieve.Methylation of FANCF is obviously higher in patient group than control group hints it probably plays a role in the pathogenesis of AML and MDS.Methylation of FANCF is obviously higher in preliminary diagnosis group than CR group hints It may be concerned with prognosis of AML and MDS,as far as has probably clinical significance in predicting prognosis of AML and MDS.