title: The cancer‑testis antigen NXF2 is activated by the hypomethylating agent decitabine in acute leukemia cells in vitro and in vivo.
abstract: Cancer‑testis antigens (CTAs) are a group of tumor‑associated antigens restricted to male germ cells under normal physiological conditions. CTAs are expressed in certain types of tumors and thus are a novel target for immunotherapy. Nuclear RNA export factor 2 (NXF2) is a CTA of which the expression pattern, regulation and clinical significance are unclear. In the present study, following treatment with a demethylating agent, decitabine, NXF2 expression was detected in the majority of the NXF2‑negative acute leukemia cell lines, but not in healthy donor samples. This finding was confirmed by western blot analysis. Eight primary acute leukemia bone marrow samples were treated with decitabine in vitro, and results showed that NXF2 expression was significantly upregulated. In another nine acute myeloid leukemia or myelodysplastic syndrome patients, it was noted that the expression of NXF2 was upregulated in all patients following the first cycle of decitabine, which suggested that NXF2 was activated by decitabine treatment in vivo. Furthermore, NXF2 expression in acute leukemia cells was demonstrated to be regulated by CpG island hypermethylation. To the best of our knowledge, this is the first study to demonstrate that NXF2 is activated by demethylation in acute leukemia cells in vitro and in vivo. NXF2 may therefore serve as a novel target for immunotherapy against acute leukemia.
authors.affiliation: Department of Hematology, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China.
authors.forename: Jihao
authors.initials: J
authors.lastname: Zhou
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Li
authors.forename: Yushi
authors.initials: Y
authors.lastname: Yao
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Gao
authors.forename: Xufeng
authors.initials: X
authors.lastname: Luo
authors.forename: Jingxin
authors.initials: J
authors.lastname: Li
authors.forename: Mengmeng
authors.initials: M
authors.lastname: Jiang
authors.forename: Minhang
authors.initials: M
authors.lastname: Zhou
authors.forename: Lili
authors.initials: L
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015153:Blotting, Western; D016022:Case-Control Studies; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D000077209:Decitabine; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D029543:Nucleocytoplasmic Transport Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000964:Antimetabolites, Antineoplastic; D029543:Nucleocytoplasmic Transport Proteins; C533515:Nxf2 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D000077209:Decitabine; D001374:Azacitidine