Exosomal circ_0006896 promotes AML progression via interaction with HDAC1 and restriction of antitumor immunity. Exosomal circ_0006896 promotes AML progression via interaction with HDAC1 and restriction of antitumor immunity

Drug resistance and immune escape continue to contribute to poor prognosis in AML. Increasing evidence suggests that exosomes play a crucial role in AML immune microenvironment. We aimed to find a functional exosomal circRNAs/lncRNA/mRNA correlating with the progression of AML patients and further analyze its underlying mechanism in AML cells and tumor microenvironment immune cells. We find a new crucial exosomal circRNA, circ_0006896, is upregulated in both AML cells and exosomes and correlates with the prognosis and relapse of AML. In vitro and in vivo studies suggest that circ_0006896 significantly promotes AML cell proliferation, reduces chemotherapy sensitivity, and more importantly, impairs the efficacy of adoptive T cell-transfer immunotherapy. Overall design: The exosomes of the bone marrow serums from 6 AML patients and 4 healthy donors were analyzed for transcriptome sequencing using IlluminaNovaSeq6000 system. Transcriptional analysis of Molm-13 cells transfected with NC-shRNA or circ_0006896-shRNA.