| First Author | Hyde RK | Year | 2015 |
| Journal | Leukemia | Volume | 29 |
| Issue | 8 | Pages | 1771-8 |
| PubMed ID | 25742748 | Mgi Jnum | J:224239 |
| Mgi Id | MGI:5661769 | Doi | 10.1038/leu.2015.58 |
| Citation | Hyde RK, et al. (2015) Runx1 is required for hematopoietic defects and leukemogenesis in Cbfb-MYH11 knock-in mice. Leukemia 29(8):1771-8 |
| abstractText | CBFbeta-SMMHC (core-binding factor beta-smooth muscle myosin heavy chain), the fusion protein generated by the chromosome 16 inversion fusion gene, CBFB-MYH11, is known to initiate leukemogenesis. However, the mechanism through which CBFbeta-SMMHC contributes to leukemia development is not well understood. Previously, it was proposed that CBFbeta-SMMHC acts by dominantly repressing the transcription factor RUNX1 (Runt-related protein 1), but we recently showed that CBFbeta-SMMHC has activities that are independent of RUNX1 repression. In addition, we showed that a modified CBFbeta-SMMHC with decreased RUNX1-binding activity accelerates leukemogenesis. These results raise questions about the importance of RUNX1 in leukemogenesis by CBFbeta-SMMHC. To test this, we generated mice expressing Cbfb-MYH11 in a Runx1-deficient background, resulting from either homozygous Runx1-null alleles (Runx1(-/-)) or a single dominant-negative Runx1 allele (Runx1(+/lz)). We found that loss of Runx1 activity rescued the differentiation defects induced by Cbfb-MYH11 during primitive hematopoiesis. During definitive hematopoiesis, RUNX1 loss also significantly reduced the proliferation and differentiation defects induced by Cbfb-MYH11. Importantly, Cbfb-MYH11-induced leukemia had much longer latency in Runx1(+/lz) mice than in Runx1-sufficient mice. These data indicate that Runx1 activity is critical for Cbfb-MYH11-induced hematopoietic defects and leukemogenesis. |
