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

Anderson, Kristina (author): Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine

Rusterholz, Corinne (author): Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine

Månsson, Robert (author): Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine

Jensen, Christina (author): Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine

Bacos, Karl (author): Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine

Zandi, Sasan (author): Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine

Sasaki, Yutaka (author): Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine

Nerlov, Claus (author): Lund University,Lunds universitet,Avdelningen för molekylärmedicin och genterapi,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Division of Molecular Medicine and Gene Therapy,Department of Laboratory Medicine,Faculty of Medicine,Stem Cell Center,Division of stem cell research

Sigvardsson, Mikael (author): Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine

Jacobsen, Sten Eirik W (author): Lund University,Lunds universitet,Stamcellscentrum (SCC),Avdelningen för stamcellsforskning,Institutionen för laboratoriemedicin,Medicinska fakulteten,Stem Cell Center,Division of stem cell research,Department of Laboratory Medicine,Faculty of Medicine

(creator_code:org_t)

2007-01-11
2007
English.
In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 109:Jan 11, s. 3697-3705

Related links:: http://www.ncbi.nlm.... (free); show more...; http://dx.doi.org/10... (free); https://lup.lub.lu.s...; https://doi.org/10.1...; show less...

Abstract Subject headings

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.

By the author/editor: Anderson, Kristi ...; Rusterholz, Cori ...; Månsson, Robert; Jensen, Christin ...; Bacos, Karl; Zandi, Sasan; show more...; Sasaki, Yutaka; Nerlov, Claus; Sigvardsson, Mik ...; Jacobsen, Sten E ...; show less...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Hematology

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