The preleukemic state of mice reconstituted with Mixl1-transduced marrow cells
Details
Publication Year 2007-12-11, Volume 104, Issue #50, Page 20013-20018
Journal Title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Publication Type
Journal Article
Abstract
Murine granulocytic cells, in becoming leukemic, need to acquire enhanced self-generation and a capacity for autocrine growth stimulation. Mice transplanted with bone marrow cells transduced with the Mixl1 homeobox gene develop a very high frequency of myeloid leukemia derived from the transduced cells. Preleukemic mice contained a high frequency of transduced clonogenic granulocytic cells. They exhibited an abnormally high capacity for self-replication and could generate immortalized granulocytic cell lines that remained absolutely dependent on either GM-CSF or IL-3 and were not leukemic. Organs from mice repopulated by marrow cells transduced either with Mixl1 or the control murine stem cell virus vector exhibited a capacity to produce IL-3 in vitro, activity being highest with the lungs, marrow, bladder, and thymus. Supporting evidence for the in vivo production of IL-3 was the frequent development of mast cells in the marrow. Overexpression of Mixl1 appears capable of inducing an abnormal self-renewal capacity in granulocytic precursors. Aberrant production of IL-3 was not present in the continuous Mixl cell lines and was therefore not in itself likely to be a leukemogenic change but it could support the enhanced survival and proliferation of the Mixl1 granulocytic populations until a final leukemogenic mutation occurs in them.
Publisher
NATL ACAD SCIENCES
Keywords
ACUTE MYELOID-LEUKEMIA; GM-CSF; HEMATOPOIETIC-CELLS
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2007-12-11 12:00:00
Last Modified: 2014-12-23 01:28:38
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