Study On The Relationship Of ZO-1Gene Methylation And The Chronic Myelocytic Leukemia Disease Stage

Background: Chronic myelocytic leukemia (CML) is also called the CML,acquired malignant cloning disease of hematopoietic stem cells, the course isdivided into chronic phase (CP), accelerated phase (AP) and blast crisis (BP/BC).Accelerated phase and blast crisis is considered as the progression of the disease,the disease incidence in the age of60-65years old. The tyrosine kinase inhibitor(TKI) become the first-line treatment of CML, the traditional view is that theCML patients in acute phase of choice for allogeneic hematopoietic stem celltransplantation, and is the only means may cure the disease. Otherwise, thecourse is only3-6months, but the cost is high and there is a risk oftransplantation. So the clinical treatment of patients in chronic phase to maintainin good, need to focus on disease progression in patients with CML when, butthere is no specific molecular marker for leukemia.Research shows that theoccurrence and development of tumor is closely associated with epigenetics,which DNA methylation is an important epigenetic regulation mechanism oftable, abnormal methylation of leukemia is a common phenomenon in theprocess of. Research shows that multiple gene methylation was found in allkinds of leukemia, suggesting that DNA methylation modification associatedwith leukemia. Previous research shows people, tight junction protein (ZO-1)gene promoter region, showing high specificity of methylation status in acuteleukemia, and acute leukemia occurrence, development and prognosis areclosely related to the prognosis of leukemia, is a bad factor.Objective: To investigate the chronic and acute leukemia cell lines and thecourse of disease in patients with CML bone marrow samples from differenttime difference analysis of CML in different periods of ZO-1gene methylation status in the promoter region, and with the stage of disease changes itsmethylation status has changed.Results:1. The promoter region of ZO-1gene showed non methylation status inK562cell line, HL-60, Molt-4cell lines showed high specific methylation status,and ZO-1in acute leukemia cell lines expressing silence.After demethylationdrug decitabine treated HL-60and Molt-4cells, ZO-1gene promotermethylation status of the transformation from high non methylation status ofZO-1gene and expression of recovery.2. ZO-1gene promoter methylation status in non normal population,patients with chronic phase of CML showed non methylation status, patientswith CML accelerated rendering specific methylation status in phase and blasticphase. Detection of CML-in10patients with CP, ZO-1gene was unmethylatedstate, the detection of CML-AP in patients with8cases,4cases (50%) showedhigh methylation status of7CML-BC patients,5cases (70%) appearedhypermethylation of ZO-1gene status.3. In1CML patients in chronic phase showed unmethylated ZO-1gene,acute period showed high methylation status, returned to the chronic phase aftermethylation can change non methylation status.Conclusion:ZO-1gene methylation status in the promoter region of CML in differentperiods are associated with. As the disease progresses, the methylation of ZO-1gene increased the proportion of high methylation status may have diseaseprogression tendency.