Biphenotypic B-lymphoid/myeloid cells expressing low levels of Pax5: potential targets of BAL development.
Blood, 2012/11/01;120(18):3688-98.
Simmons S[1], Knoll M, Drewell C, Wolf I, Mollenkopf HJ, Bouquet C, Melchers F
Affiliations
PMID: 22927250DOI: 10.1182/blood-2012-03-414821
Impact factor: 25.476
Abstract
The expression of Pax5 commits common lymphoid progenitor cells to B-lymphoid lineage differentiation. Little is known of possible variations in the levels of Pax5 expression and their influences on hematopoietic development. We have developed a retroviral transduction system that allows for the study of possible intermediate stages of this commitment by controlling the levels of Pax5 expressed in Pax5-deficient progenitors in vitro and in vivo. Retroviral transduction of Pax5-deficient pro-/pre-B cell lines with a doxycycline-inducible (TetON) form of the human Pax5 (huPax5) gene yielded cell clones that could be induced to different levels of huPax5 expression. Clones inducible to high levels developed B220(+)/CD19(+)/IgM(+) B cells, while clones with low levels differentiated to B220(+)/CD19(-)/CD11b(+)/Gr-1(-) B-lymphoid/myeloid biphenotypic cells in vitro and in vivo. Microarray analyses of genes expressed at these lower levels of huPax5 identified C/ebpα, C/ebpδ, Pu.1, Csf1r, Csf2r, and Gata-3 as myeloid-related genes selectively expressed in the pro-/pre-B cells that can develop under myeloid/lymphoid conditions to biphenotypic cells. Therefore, reduced expression of huPax5 during the induction of early lymphoid progenitors to B-lineage-committed cells can fix this cellular development at a stage that has previously been seen during embryonic development and in acute lymphoblastic lymphoma-like biphenotypic acute leukemias.
MeSH terms
Animals; B-Lymphocytes; Cell Differentiation; Cell Lineage; Cells, Cultured; Flow Cytometry; Humans; Immunoblotting; Mice; Myeloid Cells; Oligonucleotide Array Sequence Analysis; PAX5 Transcription Factor; Phenotype; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor Cells, B-Lymphoid; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; Transduction, Genetic
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