CBX8, a polycomb group protein, is essential for MLL-AF9-induced leukemogenesis.
CBX8, a polycomb group protein, is essential for MLL-AF9-induced leukemogenesis.
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DOI：
10.1016/j.ccr.2011.09.008
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发表时间：
2011-11-15
期刊：
影响因子：
50.3
通讯作者：
Hess JL
中科院分区：
文献类型：
--
作者：
Tan J;Jones M;Koseki H;Nakayama M;Muntean AG;Maillard I;Hess JL
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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