Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute myeloid leukemia.
Hope L MummeBeena E ThomasSwati S BhasinUpaasana KrishnanBhakti DwivediPruthvi PerumallaDebasree SarkarGulay B UlukayaHimalee S SabnisSunita I ParkDeborah DeRyckereSunil S RaikarMelinda PaulyRyan J SummersSharon M CastellinoDaniel S WechslerChristopher C PorterDouglas K GrahamManoj K BhasinPublished in: Nature communications (2023)
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.
Keyphrases
- acute myeloid leukemia
- single cell
- rna seq
- free survival
- allogeneic hematopoietic stem cell transplantation
- genome wide
- high throughput
- stem cells
- bone marrow
- dendritic cells
- fatty acid
- genome wide identification
- oxidative stress
- mesenchymal stem cells
- dna methylation
- systemic lupus erythematosus
- disease activity
- epithelial mesenchymal transition
- hydrogen peroxide
- gene expression
- acute lymphoblastic leukemia
- immune response
- transcription factor
- cell therapy
- replacement therapy
- genome wide analysis