Methylation status of DDIT3 gene in Chronic Myeloid Leukemia

Ya-Li Wang,Dong-Ming Yao,Jiang Lin,Zhen Qian,Zhao-Hui Zhu,Jun Qian,Jian-Yong Li

doi:10.1186/1756-9966-29-54

Ya-Li Wang, Dong-Ming Yao + Show 5 more

Open Access

https://doi.org/10.1186/1756-9966-29-54

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Abstract

BackgroundDNA-damage-inducible transcript 3 (DDIT3), a candidate tumor suppressor gene (TSG), has been found involved in the regulation of cellular growth and differentiation. The epigenetic changes of TSGs are recently recognized as an abnormal mechanism contributing to the development of chronic myeloid leukemia (CML). The aim of this study was to investigate the methylation status of DDIT3 gene in CML patients.MethodsThe methylation status of DDIT3 promoter was detected in the bone marrow mononuclear cells from 53 patients with CML using methylation-specific PCR (MSP). The expression levels of DDIT3 and bcr/abl transcript were determined by real-time quantitative PCR (RQ-PCR). Clinical data of these patients were collected and analyzed.ResultsThe aberrant methylation of DDIT3 gene promoter was found in 35 of 53 (66%) CML cases. Correlation was not found between DDIT3 promoter hypermethylation and the age, sex, hemoglobin concentration, platelet counts, chromosomal abnormalities, bcr/abl transcript, and staging of CML patients (P > 0.05), but found between DDIT3 promoter hypermethylation and WBC counts of CML cases (R = 0.781, P < 0.001). The level of DDIT3 transcript in CML patients was significantly lower than that in controls (median 3.28 vs 19.69, P < 0.001), however, there was no difference in the level of DDIT3 transcript between methylation-positive CML cases (0.05-65.32, median 2.13) and methylation- negative CML cases (0.12-126.04, median 3.92) (P > 0.05).ConclusionOur results demonstrate that aberrant methylation of DDIT3 occurs in CML frequently.

Highlights

DNA-damage-inducible transcript 3 (DDIT3), a candidate tumor suppressor gene (TSG), has been found involved in the regulation of cellular growth and differentiation
Chronic myeloid leukemia (CML) is a stem cell disease characterized by excessive accumulation of clonal myeloid cells in hematopoietic tissues
chronic myeloid leukemia (CML) can be divided into three phases: the chronic phase (CP), the accelerated phase (AP), the blast crisis (BC) [1,2]

Summary

Introduction

DNA-damage-inducible transcript 3 (DDIT3), a candidate tumor suppressor gene (TSG), has been found involved in the regulation of cellular growth and differentiation. The epigenetic changes of TSGs are recently recognized as an abnormal mechanism contributing to the development of chronic myeloid leukemia (CML). The aim of this study was to investigate the methylation status of DDIT3 gene in CML patients. Chronic myeloid leukemia (CML) is a stem cell disease characterized by excessive accumulation of clonal myeloid cells in hematopoietic tissues. Almost all patients with CML present the common cytogenetic abnormality of the t(9;22) and the bcr/abl fusion gene which is generated by the translocation. BC is the last stage of CML disease progress, in which hematopoietic differentiation become arrested and immature blasts accumulate in the bone marrow and spill into the circulation.

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