RUNX1/ETO effects on the interactions with t(8;21) AML with bone marrow niche: lessons from scRNAseq

To study the role of the RUNX1/ETO fusion in interactions of AML cells with the bone marrow niche, we co-cultured a t(8;21) AML PDX with mesenchymal stromal cells (MSC) and performed a RUNX1/ETO knockdown (KD) using a lipid nanoparticle siRNA delivery system.

Single cell RNA-seq followed by gene set enrichment analysis showed that co-culture with AML cells interfere with cell cycle-related pathways in MSCs. Knockdown of RUNX1/ETO not only restored these pathways in MSCs, but also affected multiple pathways in AML and MSCs in opposite direction. In addition to cell cycle, metabolic pathways such as glycolysis, fatty acid metabolism and amino acid metabolism were downregulated in AML cells and upregulated in MSCs. These data indicate that targeted interference with a central driver of leukaemia can have profound consequences for the transcriptional programmes of surrounding niche cells and suggest a direct role for fusion genes such as RUNX1/ETO in the dysregulation of the leukaemic niche.

Publication History

Article published online:
17 May 2022