Inactivation of PU.1 in adult mice leads to the development of myeloid leukemia
Details
Publication Year 2006-01-31, Volume 103, Issue #5, Page 1486-1491
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type
Journal Article
Abstract
Genetically primed adult C57BL mice were deleted of exon 5 of the gene encoding the transcription factor PU.1 by IFN activation of Cre recombinase. After a 13-week delay, conditionally deleted (PU.1(-/-)) mice began dying of myeloid leukemia, and 95% of the mice surviving from early postinduction death developed transplantable myeloid leukemia whose cells were deleted of PU.1 and uniformly Gr-1 positive. The leukemic cells formed autonomous colonies in semisolid culture with varying clonal efficiency, but colony formation was enhanced by IL-3 and sometimes by granulocyte-macrophage colony-stimulating factor. Nine of 13 tumors analyzed had developed a capacity for autocrine IL-3 or granulocyte-macrophage colony-stimulating factor production, and there was evidence of rearrangement of the IL-3 gene. Acquisition of autocrine growth-factor production and autonomous growth appeared to be major events in the transformation of conditionally deleted PU.1(-/-) cells to fully developed myeloid leukemic populations.
Publisher
NATL ACAD SCIENCES
Keywords
TRANSCRIPTION FACTOR PU.1; HEMATOPOIETIC STEM-CELLS; IN-VITRO; PROGENITORS; GROWTH; DIFFERENTIATION; EXPRESSION; AML; DISRUPTION; MUTATIONS
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2006-01-31 12:00:00
Last Modified: 0001-01-01 12:00:00
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