| First Author | Kamikubo Y | Year | 2013 |
| Journal | Blood | Volume | 121 |
| Issue | 4 | Pages | 638-42 |
| PubMed ID | 23152542 | Mgi Jnum | J:193140 |
| Mgi Id | MGI:5467697 | Doi | 10.1182/blood-2012-06-434688 |
| Citation | Kamikubo Y, et al. (2013) The C-terminus of CBFbeta-SMMHC is required to induce embryonic hematopoietic defects and leukemogenesis. Blood 121(4):638-42 |
| abstractText | The C-terminus of CBFbeta-SMMHC, the fusion protein produced by a chromosome 16 inversion in acute myeloid leukemia subtype M4Eo, contains domains for self-multimerization and transcriptional repression, both of which have been proposed to be important for leukemogenesis by CBFbeta-SMMHC. To test the role of the fusion protein's C-terminus in vivo, we generated knock-in mice expressing a C-terminally truncated CBFbeta-SMMHC (CBFbeta-SMMHCDeltaC95). Embryos with a single copy of CBFbeta-SMMHCDeltaC95 were viable and showed no defects in hematopoiesis, whereas embryos homozygous for the CBFbeta-SMMHCDeltaC95 allele had hematopoietic defects and died in mid-gestation, similar to embryos with a single-copy of the full-length CBFbeta-SMMHC. Importantly, unlike mice expressing full-length CBFbeta-SMMHC, none of the mice expressing CBFbeta-SMMHCDeltaC95 developed leukemia, even after treatment with a mutagen, although some of the older mice developed a nontransplantable myeloproliferative disease. Our data indicate that the CBFbeta-SMMHC's C-terminus is essential to induce embryonic hematopoietic defects and leukemogenesis. |
