| First Author | Petropoulos K | Year | 2008 |
| Journal | J Exp Med | Volume | 205 |
| Issue | 3 | Pages | 515-22 |
| PubMed ID | 18316418 | Mgi Jnum | J:163734 |
| Mgi Id | MGI:4829602 | Doi | 10.1084/jem.20071875 |
| Citation | Petropoulos K, et al. (2008) A novel role for Lef-1, a central transcription mediator of Wnt signaling, in leukemogenesis. J Exp Med 205(3):515-22 |
| abstractText | Canonical Wnt signaling is critically involved in normal hematopoietic development and the self-renewal process of hematopoietic stem cells (HSCs). Deregulation of this pathway has been linked to a large variety of cancers, including different subtypes of leukemia. Lef-1 is a major transcription factor of this pathway and plays a pivotal role in lymphoid differentiation as well as in granulopoiesis. Here, we demonstrate Lef-1 expression in murine HSCs as well as its expression in human leukemia. Mice transplanted with bone marrow retrovirally transduced to express Lef-1 or a constitutive active Lef-1 mutant showed a severe disturbance of normal hematopoietic differentiation and finally developed B lymphoblastic and acute myeloid leukemia (AML). Lef-1-induced AMLs were characterized by immunoglobulin (Ig) DH-JH rearrangements and a promiscuous expression of lymphoid and myeloid regulatory factors. Furthermore, single cell experiments and limiting dilution transplantation assays demonstrated that Lef-1-induced AML was propagated by a leukemic stem cell with lymphoid characteristics displaying Ig DH-JH rearrangements and a B220(+) myeloid marker(-) immunophenotype. These data indicate a thus far unknown role of Lef-1 in the biology of acute leukemia, pointing to the necessity of balanced Lef-1 expression for an ordered hematopoietic development. |
