Methylation Analysis Of The Wnt Antagonist In Myelodysplastic Syndrome

Background and ObjectivesMyelodysplastic syndrome (MDS) is one of the most threatening hematological malignancies. Recently, the epigenetic changes have been recognized in the MDS, and some research found that the aberrant DNA methylation had close relationship with the MDS. Meanwhile, some studies showed that the activation of the Wnt signaling pathway and abnormal methylation of the Wnt antagonists had close relationship with hematological malignancies, such as AML,ALL,CML,and CLL, but less is known in MDS. In our research, we studied the methylation status of Wnt antagonists (DKK1, DKK3, HDPR1, WIF-1, SFRPl and SFRP4) in the patients with MDS and evaluated the role of them in the pathogenesis and progression of MDS, with providing a new theory support for clarifying the complicated pathogenesis and progression of MDS.MethodsThe methylation status of Wnt antagonists (DKK1, DKK3, HDPR1, WIF-1, SFRPl and SFRP4) in pretreatment bone marrow samples from 54 patients with MDS was measured by methylation-specific polymerase chain reaction (MSP). On the other hand, we collected the clinical materials of the patients with MDS and follow up the patients. Then the correlation between methylation and clinical features as well as prognosis of MDS patients was analyzed.ResultsIn 54 bone marrow samples, the methylation frequencies of the Wnt antagonists were as follows:DKK1 for 61.1%(33/54), SFRP4 for 50.0%(27/54), HDPRl for 33.3 %(18/54), SFRP1 for 18.5%(10/54), DKK3 for.9.3%(5/54), and DKK1 for 9.3% (5/54). After analyzing individual tumor suppressor gene, clinical parameters and prognostic information, it was found that the methylation frequency of HDPR1 was significantly higher in patients with the ANC bellow 1.5×109/L than the patients with the ANC above 1.5×109/L (48.0%和15.8%, P=0.026); and the patients with the percentage of BM blast above 5%had higher methylation frequency of HDPRl than the patients with the percentage of BM blast bellow 5%(44.4%和13.3%, P=0.034); besides, the methylation frequency of HDPRl exhibited significant differences in the MDS subtypes (P=0.017), and was significantly correlated with the WPSS (P=0.013); in addition, methylation status of SFRP4 was associated with the PLT (P=0.003) and IPSS (P=0.024); however, the methylation frequency of DKK3 was significantly higher in patients above 60 years than that bellow 60 years (P=0.045), and the methylation frequency of SFRP1 was significantly higher in female (33.3%) than male (9.1%), P value was 0.035.ConclusionThe methylation of the Wnt antagonists (DKK1, DKK3, HDPR-1, WIF-1, SFRP1 and SFRP4) were observed in patients with MDS and their methylation frequencies were different. The aberrant methylation of HDPR1 may play an important role in the progression of MDS.