Study On The Methylation Status Of DDIT3 Gene Promoter In Hematologic Malignancies

Objective To investigate the methylation status of DNA-damage inducible transcription3(DDIT3) gene promoter and its clinical correlation in patients with hematologic malignancies including myelodysplastic syndrome(MDS),acute myeloid leukemia(AML) and chronic myeloid leukemia(CML).Methods The methylation-specific PCR(MSP) technique was established and used to detect the methylation status of DDIT3 promoter in the bone marrow mononuclear cells from the patients with MDS,AML and CML.Results DDIT3 promoter hypermethylation was not detected in control group,but found in patients with MDS,AML,CML.①DDIT3 promoter hypermethylation was found in 21(31.3%) MDS cases. Correlation was not found between DDIT3 promoter hypermethylation and sex,age,hematologic parameters,chromosomal abnormalities of MDS patients.The significant difference was not observed in the frequencies of DDIT3 promoter hypermethylation among the patients with refractory anemia/refractory anemia with ringed siderobisasis (RA/RAS)(1/6,16.7%),fractory cytopenia with multilineage dysplasia (RCMD) and RCMD with ringed blasts(RCMD-RS)(10/25,40.0%),RA with excess blasts-1(RAEB-1)(3/12,25.0%),RAEB-2(4/13,30.8%), 5q- syndrome(1/3,33.3%) and refractory anemia with excess blasts in transformation/acute myeloid leukemia(RAEBt/AML)(2/8,25.0%)(x~2 =1.853,P=0.869).The correlation was not observed between DDIT3 promoter hypermethylation and WHO classification,FAB classification or IPSS grouping.②DDIT3 promoter hypermethylation was found in 62 (46.6%) AML cases.There was no correlation between DDIT3 promoter hypermethylation and the sex,age,WBC counts,platelet counts, chromosomal abnormalities of AML patients(P＞0.05).However, correlation was observed between DDIT3 promoter hypermethylation and hemoglobin concentration(R=0.201,P=0.033).The hypermethylation frequencies of DDIT3 promoter in AML patients were as follows:37.5% (9/15,M1),43.2%(19/44,M2),42.6%(9/21,M3),40.9%(9/22,M4), 81.3%(13/16,M5) and 50.0%(3/6,M6).The significant difference was not observed in the frequencies of DDIT3 gene hypermethylation among patients with different subtypes(x~2=9.157,P=0.103).③DDIT3 promoter hypermethylation was found in 39(66.1%) CML cases.Correlation was not found between DDIT3 promoter hypermethylation and the age,sex, hemoglobin concentration,platelet counts,chromosomal abnormalities of CML patients(P＞0.05),but found between DDIT3 promoter hypermethylation and WBC counts of CML cases(R=0.286,P=0.033). The hypermethyllation frequences of DDIT3 promoter in CML patients at CP,AP and BC were 68.4%,100.0%,47.1%,respectively.Correlation was also not found between the frequencies of DDIT3 promoter hypermethylation and different CML stages(P＞0.05).The methylation status of DDIT3 promoter in one CML patient became positive when his disease progressed into AP and BC from CP.Conclusions DDIT3 gene hypermethylation might be involved in t the development of myeloid malignancies including MDS,AML and CML.