| First Author | Simmons S | Year | 2012 |
| Journal | Blood | Volume | 120 |
| Issue | 18 | Pages | 3688-98 |
| PubMed ID | 22927250 | Mgi Jnum | J:192936 |
| Mgi Id | MGI:5466828 | Doi | 10.1182/blood-2012-03-414821 |
| Citation | Simmons S, et al. (2012) Biphenotypic B-lymphoid/myeloid cells expressing low levels of Pax5: potential targets of BAL development. Blood 120(18):3688-98 |
| abstractText | 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/ebpalpha, C/ebpdelta, 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. |
