Immune evasion by oncogenic proteins of acute myeloid leukemia

Shlomo Elias, Rachel Yamin, Lior Golomb, Pinchas Tsukerman, Noah Stanietsky-Kaynan, Dina Ben-Yehuda, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

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 immuoprecepitation (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.

Original languageAmerican English
Pages (from-to)1535-1543
Number of pages9
JournalBlood
Volume123
Issue number10
DOIs
StatePublished - 6 Mar 2014

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