CBX8, a Polycomb Group Protein, Is Essential for MLL-AF9-Induced Leukemogenesis

Jiaying Tan, Morgan Jones, Haruhiko Koseki, Manabu Nakayama, Andrew G. Muntean, Ivan Maillard, Jay L Hess

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)563-575
Number of pages13
JournalCancer Cell
Volume20
Issue number5
DOIs
StatePublished - Nov 15 2011
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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    Tan, J., Jones, M., Koseki, H., Nakayama, M., Muntean, A. G., Maillard, I., & Hess, JL. (2011). CBX8, a Polycomb Group Protein, Is Essential for MLL-AF9-Induced Leukemogenesis. Cancer Cell, 20(5), 563-575. https://doi.org/10.1016/j.ccr.2011.09.008