Inactivation of PU.1 in adult mice leads to the development of myeloid leukemia
- Author(s)
- Metcalf, D; Dakic, A; Mifsud, S; Di Rago, L; Wu, L; Nutt, S;
- 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
- Publisher's Version
- https://doi.org/10.1073/pnas.0510616103
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2006-01-31 12:00:00