Hematopoietic overexpression of the transcription factor Erg induces lymphoid and erythro-megakaryocytic leukemia
Details
Publication Year 2012-09-18, Volume 109, Issue #38, Page 15437-15442
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type
Journal Article
Abstract
The transcription factor encoded by the E-twenty-six (ETS)-related gene, ERG, is an essential regulator of hematopoietic stem cell function and a potent human oncoprotein. Enforced expression of ERG in murine hematopoietic cells leads to the development of a well-characterized lymphoid leukemia and a less well-defined non lymphoid disease. To clarify the latter, we generated murine bone marrow chimeras with enforced Erg expression in engrafted hematopoietic progenitor cells. As expected, these mice developed lymphoid leukemia. However, the previously reported non lymphoid disease that developed was shown to be a uniform, transplantable leukemia with both erythroid and megakaryocytic characteristics. In vivo, this disease had the overall appearance of an erythroleukemia, with an accumulation of immature erythroblasts that infiltrated the bone marrow, spleen, liver, and lung. However, when stimulated in vitro, leukemic cell clones exhibited both erythroid and megakaryocytic differentiation, suggesting that transformation occurred in a bipotential progenitor. Thus, in mice, Erg overexpression induces the development of not only lymphoid leukemia but also erythro-megakaryocytic leukemia.
Publisher
NATL ACAD SCIENCES
Keywords
DOWN-SYNDROME; MYELOPROLIFERATIVE DISEASE; MEGAKARYOBLASTIC LEUKEMIA; LYMPHOBLASTIC-LEUKEMIA; MYELOID-LEUKEMIA; PROGENITOR CELLS; HIGH EXPRESSION; MOUSE MODEL; STEM-CELLS; GENE
WEHI Research Division(s)
Cancer And Haematology
Rights Notice
Copyright © 2013 National Academy of Sciences.


Creation Date: 2012-09-18 12:00:00
Last Modified: 0001-01-01 12:00:00
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