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

Hope Mumme, Beena E. Thomas, Swati S. Bhasin, Upaasana Krishnan, Bhakti Dwivedi, Pruthvi Perumalla, Debasree Sarkar, Gulay B. Ulukaya, Himalee S. Sabnis, Sunita I. Park, Deborah DeRyckere, Sunil S. Raikar, Melinda Pauly, Ryan J. Summers, Sharon M. Castellino, Daniel S. Wechsler, Christopher C. Porter, Douglas K. Graham and Manoj Bhasin ()
Additional contact information
Hope Mumme: Emory University School of Medicine
Beena E. Thomas: Children’s Healthcare of Atlanta
Swati S. Bhasin: Children’s Healthcare of Atlanta
Upaasana Krishnan: Emory University School of Medicine
Bhakti Dwivedi: Winship Cancer Institute, Emory University
Pruthvi Perumalla: Georgia Institute of Technology
Debasree Sarkar: Emory University School of Medicine
Gulay B. Ulukaya: Emory University School of Medicine
Himalee S. Sabnis: Children’s Healthcare of Atlanta
Sunita I. Park: Emory University School of Medicine
Deborah DeRyckere: Children’s Healthcare of Atlanta
Sunil S. Raikar: Children’s Healthcare of Atlanta
Melinda Pauly: Children’s Healthcare of Atlanta
Ryan J. Summers: Children’s Healthcare of Atlanta
Sharon M. Castellino: Children’s Healthcare of Atlanta
Daniel S. Wechsler: Children’s Healthcare of Atlanta
Christopher C. Porter: Children’s Healthcare of Atlanta
Douglas K. Graham: Children’s Healthcare of Atlanta
Manoj Bhasin: Emory University School of Medicine

Nature Communications, 2023, vol. 14, issue 1, 1-20

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-41994-0

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