title: EWSR1/ELF5 induces acute myeloid leukemia by inhibiting p53/p21 pathway.
abstract: The Ewing sarcoma breakpoint region 1 (EWSR1) gene is known to fuse with various partner genes to promote the development of the Ewing sarcoma family of tumors and other sarcomas. In contrast, the association of EWSR1 chimeric fusion genes with leukemia has rarely been reported. We identified a novel EWSR1-associated chimeric fusion gene in a patient with acute myeloid leukemia harboring 46, XY, t (11; 22) (p13; q12) karyotype abnormality. The patient was refractory to intensified chemotherapy including hematopoietic stem cell transplantation. Total RNA paired-end sequencing identified a novel chimeric fusion gene as EWSR1/ELF5, a member of the E26 transformation-specific transcription factor family. Transduction of EWSR1/ELF5 to NIH3T3 cells induced transformation by attenuating with the p53/p21-dependent pathway. The injection of EWSR1/ELF5-transduced NIH3T3 cells into NSG-SCID mice systematically induced the development of tumors in vivo. These results revealed the oncogenic potency of EWSR1/ELF5.
authors.affiliation: Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Akifumi
authors.initials: A
authors.lastname: Endo
authors.affiliation: Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.|Division of Leukemia and Lymphoma, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tomizawa
authors.affiliation: Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.|Department of Pediatric Oncology, National Cancer Center, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Aoki
authors.affiliation: Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Morio
authors.affiliation: Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shuki
authors.initials: S
authors.lastname: Mizutani
authors.affiliation: Department of Pediatrics and Developmental Biology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takagi
mesh_terms: D000818:Animals; D002148:Calmodulin-Binding Proteins / Q000235:genetics*; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002675:Child, Preschool; D002871:Chromosome Banding; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015470:Leukemia, Myeloid, Acute / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D009154:Mutation; D041681:NIH 3T3 Cells; D015514:Oncogene Proteins, Fusion / Q000235:genetics* / Q000378:metabolism; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins / Q000235:genetics*; D015398:Signal Transduction; D014157:Transcription Factors; D059467:Transcriptome; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D002148:Calmodulin-Binding Proteins; D004268:DNA-Binding Proteins; C116038:ELF5 protein, human; C500986:EWSR1 protein, human; D015514:Oncogene Proteins, Fusion; D050783:Proto-Oncogene Proteins c-ets; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras)
keywords: Acute myelogenous leukemia; ELF5; EWSR1; TP53; senescence