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Blood, 1 May 2007, Vol. 109, No. 9, pp. 3697-3705.
Prepublished online as a Blood First Edition Paper on January 11, 2007; DOI 10.1182/blood-2006-05-026021.
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Submitted May 31, 2006
Accepted November 19, 2006
Ectopic expression of PAX5 promotes self renewal of bi-phenotypic myeloid progenitors co-expressing myeloid and B-cell lineage associated genes
Kristina Anderson, Corinne Rusterholz, Robert Mansson, Christina T Jensen, Karl Bacos, Sasan Zandi, Yutaka Sasaki, Claus Nerlov, Mikael Sigvardsson, and Sten Eirik W Jacobsen*
Hematopoietic Stem Cell Laboratory, Lund Strategic Research Center for Stem Cell Biology & Cell Therapy, Lund University, Lund, Sweden
European Molecular Biology Laboratory, Monterotondo, Italy
Institution for Surgery and Biomedicine, Lindkoping University, Lindkoping, Sweden
* Corresponding author; email: sten.jacobsen{at}med.lu.se.
The transcription factor PAX5 is a critical regulator of B cell commitment and development. Although normally not expressed in myeloid progenitors, PAX5 has recently been shown to be frequently expressed in myeloid malignancies and to suppress expression of myeloid differentiation genes, compatible with an effect on the differentiation and/or maintenance of myeloid progenitors. However, previous studies in which PAX5 was ectopically expressed in normal myeloid progenitors in vivo and in vitro provided conflicting results as to the effect of PAX5 on myeloid development. Herein, we demonstrate that upon ectopic expression of PAX5 in bone marrow multipotent stem/progenitor cells with a bi-phenotypic B220+GR-1/MAC-1+ phenotype are produced. These remain cytokine-dependent, but unlike control-transduced cells they sustain long-term generation of myeloid progenitors in vitro, and remain capable of myeloid differentiation. Notably, PAX5+B220+GR-1/MAC-1+ myeloid progenitors co-express, at the single cell level, myeloid genes and otherwise B-cell specific PAX5 target genes. These findings establish that ectopic expression of PAX5 introduces extensive self renewal properties in otherwise short-lived myeloid progenitors. Along with the established ectopic expression of PAX5 in acute myeloid leukemia, this motivates a careful investigation of the potential involvement of ectopic PAX5 expression in myeloid and bi-phenotypic leukemias.
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