| First Author | Kamikubo Y | Year | 2010 |
| Journal | Cancer Cell | Volume | 17 |
| Issue | 5 | Pages | 455-68 |
| PubMed ID | 20478528 | Mgi Jnum | J:160522 |
| Mgi Id | MGI:4454577 | Doi | 10.1016/j.ccr.2010.03.022 |
| Citation | Kamikubo Y, et al. (2010) Accelerated leukemogenesis by truncated CBF beta-SMMHC defective in high-affinity binding with RUNX1. Cancer Cell 17(5):455-68 |
| abstractText | Dominant RUNX1 inhibition has been proposed as a common pathway for CBF leukemia. CBF beta-SMMHC, a fusion protein in human acute myeloid leukemia (AML), dominantly inhibits RUNX1 largely through its RUNX1 high-affinity binding domain (HABD). However, the type I CBF beta-SMMHC fusion in AML patients lacks HABD. Here, we report that the type I CBF beta-SMMHC protein binds RUNX1 inefficiently. Knockin mice expressing CBF beta-SMMHC with a HABD deletion developed leukemia quickly, even though hematopoietic defects associated with Runx1-inhibition were partially rescued. A larger pool of leukemia-initiating cells, increased MN1 expression, and retention of RUNX1 phosphorylation are potential mechanisms for accelerated leukemia development in these mice. Our data suggest that RUNX1 dominant inhibition may not be a critical step for leukemogenesis by CBF beta-SMMHC. |
