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Updated: Jun 21, 2026
Modeling Chemotherapy Resistant Leukemia In Vitro
Published on: February 9, 2016
Single-cell analysis reveals altered tumor microenvironments of relapse- and remission-associated pediatric acute
Hope Mumme1, Beena E Thomas2,3, Swati S Bhasin2,3
1Department of Biomedical Informatics, Emory University School of Medicine, Atlanta, GA, USA.
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.
Insights
This study reveals key differences in pediatric acute myeloid leukemia (AML) bone marrow microenvironments at diagnosis and relapse. Understanding these cellular and genetic changes offers insights into treatment resistance and remission.
Area of Science:
- Hematology
- Oncology
- Immunology
Background:
- The bone marrow microenvironment in acute myeloid leukemia (AML) varies significantly across subtypes.
- Understanding these microenvironmental differences is crucial for pediatric AML treatment.
Purpose of the Study:
- To characterize the pediatric AML bone marrow microenvironment at diagnosis, end of induction, and relapse using single-cell RNA sequencing.
- To identify molecular and cellular distinctions associated with treatment response and relapse.
Main Methods:
- Single-cell RNA sequencing (scRNA-seq) of pediatric AML bone marrow samples.
- Analysis of diagnosis, end of induction, and relapse timepoints.
- Validation of a novel 7-gene AML blast signature on independent datasets.
Main Results:
- Identified a 7-gene signature (CLEC11A, PRAME, AZU1, NREP, ARMH1, C1QBP, TRH) associated with AML blasts.
- Discovered distinct AML blast clusters linked to relapse versus continuous complete remission (CCR).
- Observed differences in T-cell exhaustion and macrophage polarization at diagnosis, and altered gene expression in residual blasts post-therapy.
Conclusions:
- Pediatric AML relapse is associated with specific immune cell profiles and blast gene expression.
- Residual leukemia cells post-therapy show overexpression of fatty acid oxidation, tumor growth, and stemness genes.
- This research provides critical insights into the pediatric AML bone marrow microenvironment, informing future therapeutic strategies.
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