| First Author | Müller AM | Year | 2008 |
| Journal | Oncogene | Volume | 27 |
| Issue | 44 | Pages | 5759-73 |
| PubMed ID | 18604246 | Mgi Jnum | J:140063 |
| Mgi Id | MGI:3811693 | Doi | 10.1038/onc.2008.196 |
| Citation | Muller AM, et al. (2008) Complementing mutations in core binding factor leukemias: from mouse models to clinical applications. Oncogene 27(44):5759-73 |
| abstractText | A great proportion of acute myeloid leukemias (AMLs) display cytogenetic abnormalities including chromosomal aberrations and/or submicroscopic mutations. These abnormalities significantly influence the prognosis of the disease. Hence, a thorough genetic work-up is an essential constituent of standard diagnostic procedures. Core binding factor (CBF) leukemias denote AMLs with chromosomal aberrations disrupting one of the CBF transcription factor genes; the most common examples are translocation t(8;21) and inversion inv(16), which result in the generation of the AML1-ETO and CBFbeta-MYH11 fusion proteins, respectively. However, in murine models, these alterations alone do not suffice to generate full-blown leukemia, but rather, complementary events are required. In fact, a substantial proportion of primary CBF leukemias display additional activating mutations, mostly of the receptor tyrosine kinase (RTK) c-KIT. The awareness of the impact and prognostic relevance of these 'second hits' is increasing with a wider range of mutations tested in clinical trials. Furthermore, novel agents targeting RTKs are emanating rapidly and entering therapeutic regimens. Here, we present a concise review on complementing mutations in CBF leukemias including pathophysiology, mouse models, and clinical implications. |
