Ectopic expression of PAX5 promotes self renewal of bi-phenotypic myeloid progenitors co-expressing myeloid and B-cell lineage associated genes.

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Abstract

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 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 on ectopic expression of PAX5 in bone marrow multipotent stem/progenitor cells, cells with a biphenotypic 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 coexpress, 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 biphenotypic leukemias.

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Subject classification (UKÄ) – MANDATORY

  • Hematology
Original languageEnglish
Pages (from-to)3697-3705
JournalBlood
Volume109
Issue numberJan 11
Publication statusPublished - 2007
Publication categoryResearch
Peer-reviewedYes

Bibliographic note

The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Stem Cell Center (013041110), Division of Molecular Medicine and Gene Therapy (013022010), Molecular Metabolism (013212001)

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Anderson, K., 2007, Hematopoietic Stem Cell Laboratory. 2001 p.

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