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.

Keywords::

• Reprimo
• pediatric acute myeloid leukemia
• hypermethylation
• tumor suppressor
• apoptosis pcr array

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Supplementary material available online

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