Single-Cell Analysis Reveals Altered Tumor Microenvironments of Relapse/ Refractory and Remission-Associated Acute Myeloid Leukemia Treated By ABC-14 Regimen

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The preliminary study (2023 ASH Poster #1522) demonstrated that ABC-14 regimen (Azacitidine, Venetoclax, and Chidamide) was comparable to “3+7” regimen in the induction therapy of newly diagnosed AML, while overcoming the limitations of drug resistance of VA regimen (Azacitidine and Venetoclax), even with better for the subtype of AML-M4/M5, and reducing the toxicity of the traditional “3+7” regimen. However, it is important to identify deeper characterization of the disease that can be used to better guide ABC-14 regimen therapy decisions and improve clinical outcomes. Here, we utilize single-cell RNA sequencing (scRNA-seq) to analyze AML bone marrow (BM) samples from diagnosis (6 cases), remission (3 cases), short time relapse (2 cases), and refractory (4 cases) timepoints, which provide insights into AML tumor and microenvironment. Bone marrow samples aspirates from AML patients and healthy individuals were obtained from the Guangdong Provincial People's Hospital under ethical guidelines with informed consent. scRNA-seq data analysis including cell clustering and cell-type annotation, CNV estimation in single cells, differentially expressed genes (DEGs) testing, GO/KEGG enrichment analysis. We focused on the distinct clusters of primary refractories, short time relapse, and continuous complete remission (CCR) associated AML blasts, monocytes, T cells, and macrophages with differential expression of genes. Relapse-associated group have more CD16+Mono, exhausted TIGIT+CD8+T cells and C1QB+macrophages, while CCR-associated group have more CD14+IFIT1+Mono, CD14+S100A12+Mono, CD14+HLA-DPB1+Mono, CD14+AQP9+Mono. Post-therapy residual blasts and primary refractory group exhibits downregulation of signal transduction by p53 class mediator genes. Also, a post-therapy T-cell cluster associated with relapse group exhibits downregulation of antigen processing and presentation of peptide antigen via MHC Class II and T-cell activation genes. Altogether, this study characterizes ABC-14 regiment treated AML relapsed /refractory and CCR associated groups to provide insights into the BM microenvironment landscape. Our results will facilitate a better understanding and the development of novel therapeutic strategies for relapsed/refractory AML patients.

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