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Publication : CBX8, a polycomb group protein, is essential for MLL-AF9-induced leukemogenesis.

First Author  Tan J Year  2011
Journal  Cancer Cell Volume  20
Issue  5 Pages  563-75
PubMed ID  22094252 Mgi Jnum  J:178955
Mgi Id  MGI:5300668 Doi  10.1016/j.ccr.2011.09.008
Citation  Tan J, et al. (2011) CBX8, a Polycomb Group Protein, Is Essential for MLL-AF9-Induced Leukemogenesis. Cancer Cell 20(5):563-75
abstractText  Chromosomal translocations involving the mixed lineage leukemia (MLL) gene lead to the development of acute leukemias. Constitutive HOX gene activation by MLL fusion proteins is required for MLL-mediated leukemogenesis; however, the underlying mechanisms remain elusive. Here, we show that chromobox homolog 8 (CBX8), a Polycomb Group protein that interacts with MLL-AF9 and TIP60, is required for MLL-AF9-induced transcriptional activation and leukemogenesis. Conversely, both CBX8 ablation and specific disruption of the CBX8 interaction by point mutations in MLL-AF9 abrogate HOX gene upregulation and abolish MLL-AF9 leukemic transformation. Surprisingly, Cbx8-deficient mice are viable and display no apparent hematopoietic defects. Together, our findings demonstrate that CBX8 plays an essential role in MLL-AF9 transcriptional regulation and leukemogenesis.
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