Open AccessEpigenetic inactivation of PLCD1 in chronic myeloid leukemia
Author(s) -
Jun-Jun Song,
Qiong Liu,
Ying Li,
Yang Zhou,
Yang Li,
Tingxiu Xiang,
Guosheng Ren,
Jianbin Chen
Publication year - 2012
Publication title -
international journal of molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.048
H-Index - 90
eISSN - 1791-244X
pISSN - 1107-3756
DOI - 10.3892/ijmm.2012.970
Subject(s) - biology , k562 cells , myeloid leukemia , cancer research , dna methylation , oncogene , cpg site , epigenetics , cell cycle , bone marrow , ectopic expression , methylation , leukemia , microbiology and biotechnology , cell , immunology , gene expression , cell culture , gene , genetics
Phospholipase C δ1 (PLCD1), is located at the important tumor suppressorlocus 3p22. It encodes an enzyme that mediates regulatory signaling of energymetabolism, calcium homeostasis and intracellular movements. PLCD1 has been studiedin some human solid tumors relating to the CpG island methylation of the genepromoter as a functional tumor suppressor. However, no such information is availablein chronic myeloid leukemia (CML). In this study, we investigated PLCD1 expressionin the CML K562 cell line (0/1) and 15% (2/13) of bone marrow mononuclear cellswith CML by using semi-quantitative PCR. The CpG island (CGI) methylation statusof the PLCD1 promoter was detected in K562 (0/1) and 56% (23/41) of CML patientsby methylation-specific PCR (MSP), but not in the normal adult bone marrow mononuclearcells. Furthermore, the DNA demethylation agent 5'-aza-2'deoxycytidine restoredthe expression of PLCD1 in K562 cells. Functional studies showed that ectopicexpression of PLCD1 in K562 cells was able to dramatically inhibit their colonyformation and induce cell cycle G1 arrest, suggesting that PLCD1 acts as a functionaltumor suppressor and may serve as a biomarker for possible early detection andprognosis of CML.