CORE BINDING FACTOR FUSION DOWNREGULATION OF ADAR2 RNA EDITING CONTRIBUTES TO AML LEUKEMOGENESIS

Abstract

Adenosine to inosine (A-to-I) RNA editing, which is catalyzed by adenosine deaminases acting on RNA (ADAR) family of enzymes ADAR1 and ADAR2, has been shown to contribute to the development and progression of multiple cancers. However, other than CML blast crisis, relatively little is known about its role in other types of AML. Here, we found that ADAR2, but not ADAR1 and ADAR3, is specifically downregulated in the core binding factor AML with t(8;21) or inv(16) translocations. In t(8;21) AML, RUNX1-driven transcription of ADAR2 was found to be repressed by the RUNX1-ETO AE9a fusion protein. Expression of two ADAR2-regulated RNA editing targets COPA and COG3 inhibited clonogenic growth of human t(8;21) AML cells. Further in vivo studies confirmed that ADAR2 could suppress leukemogenesis of t(8;21) AML through its RNA binding and editing capabilities. Our results suggest a novel finding that loss of RNA editing contributes to core binding factor AMLs.