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The Ewing sarcoma breakpoint region 1 (  EWSR 1 ) 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   EWSR 1  chimeric fusion genes with leukemia has rarely been reported. We identified a novel   EWSR 1 ‐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   EWSR 1/ ELF 5 , a member of the E26 transformation‐specific transcription factor family. Transduction of   EWSR 1/ ELF 5  to  NIH 3T3 cells induced transformation by attenuating with the p53/p21‐dependent pathway. The injection of   EWSR 1/ ELF 5‐ transduced  NIH 3T3 cells into  NSG ‐ SCID  mice systematically induced the development of tumors  in vivo . These results revealed the oncogenic potency of   EWSR 1/ ELF 5 .

EWSR 1/ ELF 5 induces acute myeloid leukemia by inhibiting p53/p21 pathway