| Autor: |
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, Manoj Bhasin |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
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| Zdroj: |
Nature Communications, Vol 14, Iss 1, Pp 1-20 (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2041-1723 |
| DOI: |
10.1038/s41467-023-41994-0 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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