ArticleBlood2021
Single-cell RNA-seq reveals developmental plasticity with coexisting oncogenic states and immune evasion programs in ETP-ALL.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 92 citations in OpenAlex.
- Cell plasticity in cancer and therapy resistance.Experimental & molecular medicine · 2026Review
- The PI3K/AKT signaling networks in cancer glucose metabolism: mechanisms and therapeutic implications.Translational oncology · 2026Review
- Co-option of lineage plasticity as a hallmark of multipotent acute leukemias.Blood neoplasia · 2026Review
- RNA Sequencing Technologies in Acute Lymphoblastic Leukemia: A Comparative Technical Review.Current issues in molecular biology · 2026Review
- Article
- Single-cell transcriptomics reveals diversity and conservation of chicken lymphocytes.Poultry science · 2026Article
- Altered immune and treatment response gene expression signatures among poverty-exposed children with B-ALL.bioRxiv : the preprint server for biology · 2026Article
- ASS1 facilitates T-ALL progression via the arginine-mediated mTORC1/c-Myc signaling pathway.Scientific reports · 2025Article
- Emerging genomic biomarkers in diagnosis and classification of T-cell acute lymphoblastic leukemia.Hematology. American Society of Hematology. Education Program · 2025Review
- Single-cell transcriptome analysis defines novel molecular subtypes and reveals therapeutic implications of T/myeloid mixed-phenotype acute leukemia.Genome medicine · 2025Article
- The role of immune checkpoints in modulating cancer stem cells anti-tumor immune responses: implications and perspectives in cancer therapy.Journal of experimental & clinical cancer research : CR · 2025Review
- FEN1 plays a key role in the transition from HSIL to CSCC.Scientific reports · 2025Article
- Multi-omics integration analysis identifies INPP4B as a T-cell-specific activation suppressor.Clinical and translational medicine · 2025Article
- NOTCH1 dimeric signaling is essential for T-cell leukemogenesis and leukemia maintenance.Blood · 2025Article
- Identification of leukemia-enriched signature through the development of a comprehensive pediatric single-cell atlas.Nature communications · 2025Article
- Native stem cell transcriptional circuits define cardinal features of high-risk leukemia.The Journal of experimental medicine · 2025Article
- Deciphering IGH rearrangement complexity and detection strategies in acute lymphoblastic leukaemia.NPJ precision oncology · 2025Review
- Single-Cell Multiomics Reveals TCR Clonotype-Specific Phenotype and Stemness Heterogeneity of T-ALL Cells.Cell proliferation · 2025Article
- Targeting WDR5/ATAD2 signaling by the CK2/IKAROS axis demonstrates therapeutic efficacy in T-ALL.Blood · 2025Article
- Genome-wide CRISPR screen identifies IRF1 and TFAP4 as transcriptional regulators of Galectin-9 in T cell acute lymphoblastic leukemia.Science advances · 2025Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors at 5 institutions in 2 countries.
Funding
Abstract
Lineage plasticity and stemness have been invoked as causes of therapy resistance in cancer, because these flexible states allow cancer cells to dedifferentiate and alter their dependencies. We investigated such resistance mechanisms in relapsed/refractory early T-cell progenitor acute lymphoblastic leukemia (ETP-ALL) carrying activating NOTCH1 mutations via full-length single-cell RNA sequencing (scRNA-seq) of malignant and microenvironmental cells. We identified 2 highly distinct stem-like states that critically differed with regard to cell cycle and oncogenic signaling. Fast-cycling stem-like leukemia cells demonstrated Notch activation and were effectively eliminated in patients by Notch inhibition, whereas slow-cycling stem-like cells were Notch independent and rather relied on PI3K signaling, likely explaining the poor efficacy of Notch inhibition in this disease. Remarkably, we found that both stem-like states could differentiate into a more mature leukemia state with prominent immunomodulatory functions, including high expression of the LGALS9 checkpoint molecule. These cells promoted an immunosuppressive leukemia ecosystem with clonal accumulation of dysfunctional CD8+ T cells that expressed HAVCR2, the cognate receptor for LGALS9. Our study identified complex interactions between signaling programs, cellular plasticity, and immune programs that characterize ETP-ALL, illustrating the multidimensionality of tumor heterogeneity. In this scenario, combination therapies targeting diverse oncogenic states and the immune ecosystem seem most promising to successfully eliminate tumor cells that escape treatment through coexisting transcriptional programs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.