title: tp53-dependent G2 arrest mediator candidate gene, Reprimo, is down-regulated by promoter hypermethylation in pediatric acute myeloid leukemia.
abstract: Reprimo (RPRM) is a novel tumor suppressor. However, the expression and molecular function of RPRM in pediatric acute myeloid leukemia (AML) is still unknown. We observed hypermethylation of the RPRM promoter in 8/11 leukemia cell lines and in 44.8% (47/105) of pediatric AML samples compared with 6.7% (2/30) of control samples. Bisulfite genomic sequencing analysis showed that the RPRM promoter was methylated in the majority of AML samples (66.2-83.1%), whereas RPRM was almost unmethylated in normal bone marrow samples (20.0-27.7%). Kaplan-Meier survival analysis revealed poor survival outcomes in samples with RPRM promoter methylation (p < 0.001). Proliferation of AML cells was inhibited in a dose-dependent manner (p < 0.05) after RPRM overexpression with lentivirus transfection. Apoptosis was up-regulated in RPRM-overexpressing AML cells. Real-time polymerase chain reaction array analysis revealed 50 dysregulated genes that might be implicated in apoptosis of RPRM-induced AML cells. RPRM may be a putative tumor suppressor in pediatric AML.
authors: a Department of Hematology and Oncology , Children's Hospital of Soochow University , Suzhou , China.
authors: Yan-Fang
authors: YF
authors: Tao
authors: a Department of Hematology and Oncology , Children's Hospital of Soochow University , Suzhou , China.
authors: Zhi-Heng
authors: ZH
authors: Li
authors: a Department of Hematology and Oncology , Children's Hospital of Soochow University , Suzhou , China.
authors: Na-Na
authors: NN
authors: Wang
authors: a Department of Hematology and Oncology , Children's Hospital of Soochow University , Suzhou , China.
authors: Fang
authors: F
authors: Fang
authors: a Department of Hematology and Oncology , Children's Hospital of Soochow University , Suzhou , China.
authors: Li-Xiao
authors: LX
authors: Xu
authors: a Department of Hematology and Oncology , Children's Hospital of Soochow University , Suzhou , China.
authors: Jian
authors: J
authors: Pan
mesh_terms: D000293:Adolescent; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D019175:DNA Methylation; D015536:Down-Regulation; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015973:Gene Expression Regulation, Leukemic; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D053208:Kaplan-Meier Estimate; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D011379:Prognosis; D011401:Promoter Regions, Genetic; D016016:Proportional Hazards Models
chemical_list: D051017:Apoptosis Regulatory Proteins; D018797:Cell Cycle Proteins; D006023:Glycoproteins; C412566:RPRM protein, human
keywords: Reprimo; apoptosis pcr array; hypermethylation; pediatric acute myeloid leukemia; tumor suppressor