| First Author | Smeenk L | Year | 2017 |
| Journal | EMBO J | Volume | 36 |
| Issue | 6 | Pages | 718-735 |
| PubMed ID | 28219927 | Mgi Jnum | J:241652 |
| Mgi Id | MGI:5903337 | Doi | 10.15252/embj.201695495 |
| Citation | Smeenk L, et al. (2017) Molecular role of the PAX5-ETV6 oncoprotein in promoting B-cell acute lymphoblastic leukemia. EMBO J 36(6):718-735 |
| abstractText | PAX5 is a tumor suppressor in B-ALL, while the role of PAX5 fusion proteins in B-ALL development is largely unknown. Here, we studied the function of PAX5-ETV6 and PAX5-FOXP1 in mice expressing these proteins from the Pax5 locus. Both proteins arrested B-lymphopoiesis at the pro-B to pre-B-cell transition and, contrary to their proposed dominant-negative role, did not interfere with the expression of most regulated Pax5 target genes. Pax5-Etv6, but not Pax5-Foxp1, cooperated with loss of the Cdkna2a/b tumor suppressors in promoting B-ALL development. Regulated Pax5-Etv6 target genes identified in these B-ALLs encode proteins implicated in pre-B-cell receptor (BCR) signaling and migration/adhesion, which could contribute to the proliferation, survival, and tissue infiltration of leukemic B cells. Together with similar observations made in human PAX5-ETV6+ B-ALLs, these data identified PAX5-ETV6 as a potent oncoprotein that drives B-cell leukemia development. |
