Open AccessEWSR 1/ ELF 5 induces acute myeloid leukemia by inhibiting p53/p21 pathway
Author(s) -
Endo Akifumi,
Tomizawa Daisuke,
Aoki Yuki,
Morio Tomohiro,
Mizutani Shuki,
Takagi Masatoshi
Publication year - 2016
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13080
Subject(s) - fusion gene , myeloid leukemia , cancer research , leukemia , biology , haematopoiesis , fusion protein , chromosomal translocation , gene , myeloid , stem cell , immunology , genetics , recombinant dna
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 .