Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia

• Authors: Hope Mumme, Emory University; Beena/Elizabeth Thomas, Emory University; Swati Sharma Bhasin, Emory University; Upaasana Krishnan, Emory University; Bhakti Dwivedi, Emory University; Pruthvi Perumalla, Georgia Institute of Technology; Debasree Sarkar, Emory University; Gulay B. Ulukaya, Emory University; Himalee Sabnis, Emory University; Sunita I. Park, Emory University; Deborah DeRyckere, Emory University; Sunil Raikar, Emory University; Melinda Pauly, Emory University; Ryan J Summers, Emory University; Sharon M. Castellino, Emory University; Daniel S. Wechsler, Emory University; Christopher Porter, Emory University; Doug Graham, Emory University; Manoj Bhasin, Emory University
• Journal Title: Nature Communications
• Volume: Volume 14
• Publisher: Springer Nature | 2023-10-05, Pages 6209-None
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1038/s41467-023-41994-0
• Subjects: Health Sciences, Oncology; Biology, Molecular
• Keywords: Acute myeloid leukaemia; Cancer genomics; Paediatric cancer; Tumour heterogeneity; Cancer microenvironment

Abstract

Acute myeloid leukemia (AML) microenvironment exhibits cellular and molecular differences among various subtypes. Here, we utilize single-cell RNA sequencing (scRNA-seq) to analyze pediatric AML bone marrow (BM) samples from diagnosis (Dx), end of induction (EOI), and relapse timepoints. Analysis of Dx, EOI scRNA-seq, and TARGET AML RNA-seq datasets reveals an AML blasts-associated 7-gene signature (CLEC11A, PRAME, AZU1, NREP, ARMH1, C1QBP, TRH), which we validate on independent datasets. The analysis reveals distinct clusters of Dx relapse- and continuous complete remission (CCR)-associated AML-blasts with differential expression of genes associated with survival. At Dx, relapse-associated samples have more exhausted T cells while CCR-associated samples have more inflammatory M1 macrophages. Post-therapy EOI residual blasts overexpress fatty acid oxidation, tumor growth, and stemness genes. Also, a post-therapy T-cell cluster associated with relapse samples exhibits downregulation of MHC Class I and T-cell regulatory genes. Altogether, this study deeply characterizes pediatric AML relapse- and CCR-associated samples to provide insights into the BM microenvironment landscape.