[PDF][PDF] CBX8, a polycomb group protein, is essential for MLL-AF9-induced leukemogenesis
J Tan, M Jones, H Koseki, M Nakayama, AG Muntean… - Cancer cell, 2011 - cell.com
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 …
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 …
Summary
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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