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Blood. 2014 Mar 6;123(10):1535-43. doi: 10.1182/blood-2013-09-526590. Epub 2014 Jan 21.

Immune evasion by oncogenic proteins of acute myeloid leukemia.

Author information

1
The Lautenberg Center for General and Tumor Immunology, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel;

Abstract

PML-RARA and AML1-ETO are important oncogenic fusion proteins that play a central role in transformation to acute myeloid leukemia (AML). Whether these fusion proteins render the tumor cells with immune evasion properties is unknown. Here we show that both oncogenic proteins specifically downregulate the expression of CD48, a ligand of the natural killer (NK) cell activating receptor 2B4, thereby leading to decreased killing by NK cells. We demonstrate that this process is histone deacetylase (HDAC)-dependent, that it is mediated through the downregulation of CD48 messenger RNA, and that treatment with HDAC inhibitors (HDACi) restores the expression of CD48. Furthermore, by using chromatin immunoprecepitation (ChIP) experiments, we show that AML1-ETO directly interacts with CD48. Finally, we show that AML patients who are carrying these specific translocations have low expression of CD48.

PMID:
24449212
PMCID:
PMC3981677
DOI:
10.1182/blood-2013-09-526590
[Indexed for MEDLINE]
Free PMC Article
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