Cancer cells possess traits reminiscent of those ascribed to normal stem ceils,including enhanced proliferation and the capacity for self-renewal.The homeodomain protein,NANOG,is critical for maintaining the self-renewal and proliferative properties of embryonic stem cells (ESCs).The abnormal expression and oncogenic potential of NANOG have been observed in multiple human tumors.However,its potential implication in leukemogenesis has not been fully clarified.In this study,we provide compelling evidence that cultured T-cell acute lymphoblastie leukemia (T-ALL) cells,as well as human primary T-ALL cells,express a functional variant of NANOG.In leukemic cells,NANOG mRNA is derived predominantly from a retrogene locus termed NANOGP8.Functional analysis revealed that RNA interference-mediated NANOG knockdown reduced cell proliferation in leukemic cells.In addition,we found that down-regulation of NANOG promoted apoptosis and induced cell cycle arrest at G0/G1 in leukemic cells.Importantly,the up-regulation of p53 and CDKN2A,and the down-regulation of MDM2,were detected in leukemic cells in which NANOG was down-regulated.Moreover,some downstream genes of p53 that function in cell cycle control or apoptosis pathways were involved in the regulation of leukemic cells by NANOG.Taken together,our results indicate that a variant of the ESC self-renewal gene,NANOG,modulates the biological function of human T-ALL cells through a p53-mediated pathway.