EWSR1/ELF5 induces acute myeloid leukemia by inhibiting p53/p21 pathway
نویسندگان
چکیده
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.
منابع مشابه
Effect of Cassiopea andromeda Venom on P15INK4b, P21 WAF1/CIP1, P53, DNA methyltransferase 1, and Bcl-2 Genes Expression, Apoptosis Induction, and Cell Growth Inhibition in Acute Promyelocytic Leukemia NB4 Cell line
Background: One of the acute hematologic malignancies is acute promyelocytic leukemia (APL) that resulted in translocation of chromosomes 15 and 17, t (15; 17), and cessation in the maturation of myeloid cell line, and ultimate aggregation of neoplastic promyelocytes. Regarding that appetence of using herbal and marine medicine studies is increasing, and on the other hand, the features of Cassi...
متن کاملThe novel tryptamine derivative JNJ-26854165 induces wild-type p53- and E2F1-mediated apoptosis in acute myeloid and lymphoid leukemias.
The development of small-molecule activators of p53 is currently focused on malignancies containing a wild-type p53 genotype, which is present in most leukemias. JNJ-26854165 is one such p53-activating agent, but its mechanism of action remains to be elucidated. Here, we report the effects of JNJ-26854165 in acute leukemias. JNJ-26854165 treatment induced p53-mediated apoptosis in acute leukemi...
متن کاملNovel Tryptamine Derivative JNJ-26854165 Induces -Type p53- and E2F1-Mediated Apoptosis in Ther te Myeloid and Lymphoid Leukemias
wnloaded development of small-molecule activators of p53 is currently focused on malignancies containing a ype p53 genotype, which is present in most leukemias. JNJ-26854165 is one such p53-activating agent, mechanism of action remains to be elucidated. Here, we report the effects of JNJ-26854165 in acute ias. JNJ-26854165 treatment induced p53-mediated apoptosis in acute leukemia cells with wi...
متن کاملMDM2 T309G has a synergistic effect with P21 ser31arg single nucleotide polymorphisms on the risk of acute myeloid leukemia.
BACKGROUND The P53 tumor suppressor gene plays a pivotal role in maintaining cellular homeostasis by preventing the propagation of genome mutations. P53 in its transcriptionally active form is capable of activating distinct target genes that contribute to either apoptosis or growth arrest, like P21. However, the MDM2 gene is a major negative regulator of P53. Single nucleotide polymorphisms (SN...
متن کاملp53 causes butein-mediated apoptosis of chronic myeloid leukemia cells
Progression of chronic myeloid leukemia, marked by the oncogenic Bcr‑Abl mutation, is tightly associated with an alteration of the p53 pathway. It is known that butein extracted from various plants represses cancer growth. Although the anticancer effects of butein are widely accepted, the mechanisms by which butein induces apoptosis of chronic myeloid leukemia cells remains to be elucidated. Th...
متن کامل