ERG Is a Megakaryocytic Oncogene

Ets-related gene (ERG) is a member of the ETS transcription factor gene family located on Hsa21. ERG is known to have a crucial role in establishing definitive hematopoiesis and is required for normal megakaryopoiesis. Truncated forms of ERG are associated with multiple cancers such as Ewing's...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2009-06, Vol.69 (11), p.4665-4673
Main Authors: SALEK-ARDAKANI, Samira, SMOOHA, Gil, DE BOER, Jasper, SEBIRE, Neil J, MORROW, Michelle, RAINIS, Liat, LEE, Sandy, WILLIAMS, Owen, IZRAELI, Shai, BRADY, Hugh J. M
Format: Article
Language:English
Subjects:
Animals
Antineoplastic agents
Biological and medical sciences
Cell Differentiation - genetics
Cell Proliferation
Cells, Cultured
Embryo, Mammalian
Hematopoietic Stem Cells - drug effects
Hematopoietic Stem Cells - metabolism
Hematopoietic Stem Cells - physiology
Humans
Interleukin-3 - pharmacology
Leukemia, Megakaryoblastic, Acute - genetics
Medical sciences
Megakaryocytes - drug effects
Megakaryocytes - metabolism
Megakaryocytes - physiology
Mice
Mice, Inbred C57BL
Mice, Transgenic
Oncogenes - physiology
Pharmacology. Drug treatments
Thrombopoiesis - drug effects
Thrombopoiesis - genetics
Trans-Activators - genetics
Trans-Activators - metabolism
Trans-Activators - physiology
Transcriptional Regulator ERG
Tumors
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Summary:Ets-related gene (ERG) is a member of the ETS transcription factor gene family located on Hsa21. ERG is known to have a crucial role in establishing definitive hematopoiesis and is required for normal megakaryopoiesis. Truncated forms of ERG are associated with multiple cancers such as Ewing's sarcoma, prostate cancer, and leukemia as part of oncogenic fusion translocations. Increased expression of ERG is highly indicative of poor prognosis in acute myeloid leukemia and ERG is expressed in acute megakaryoblastic leukemia (AMKL); however, it is unclear if expression of ERG per se has a leukemogenic activity. We show that ectopic expression of ERG in fetal hematopoietic progenitors promotes megakaryopoiesis and that ERG alone acts as a potent oncogene in vivo leading to rapid onset of leukemia in mice. We observe that the endogenous ERG is required for the proliferation and maintenance of AMKL cell lines. ERG also strongly cooperates with the GATA1s mutated protein, found in Down syndrome AMKL, to immortalize megakaryocyte progenitors, suggesting that the additional copy of ERG in trisomy 21 may have a role in Down syndrome AMKL. These data suggest that ERG is a hematopoietic oncogene that may play a direct role in myeloid leukemia pathogenesis.
ISSN:0008-5472
1538-7445
DOI:10.1158/0008-5472.CAN-09-0075