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Single cell RNA-seq reveals developmental plasticity with coexisting oncogenic states and immune evasion programs in ETP-ALL [Patients_TALLs_scRNA-seq]

ABSTRACT: Single cell RNA-seq reveals developmental plasticity with coexisting oncogenic states and immune evasion programs in ETP-ALL [Patients_TALLs_scRNA-seq]

PROVIDER: PRJNA679818 | ENA |

REPOSITORIES: ENA

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Single cell RNA-seq reveals developmental plasticity with coexisting oncogenic states and immune evasion programs in ETP-ALL

Project description:Single cell RNA-seq reveals developmental plasticity with coexisting oncogenic states and immune evasion programs in ETP-ALL

| PRJNA679811 | ENA

Single cell RNA-seq reveals developmental plasticity with coexisting oncogenic states and immune evasion programs in ETP-ALL [PDX_ETPs_scRNA-seq]

Project description:Single cell RNA-seq reveals developmental plasticity with coexisting oncogenic states and immune evasion programs in ETP-ALL [PDX_ETPs_scRNA-seq]

| PRJNA679819 | ENA

Single-cell RNA-seq reveals developmental plasticity with coexisting oncogenic states and immune evasion programs in ETP-ALL.

Project description: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.

| S-EPMC8109012 | biostudies-literature

Single cell RNA-seq reveals developmental plasticity with coexisting oncogenic states and immune evasion programs in ETP-ALL

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-01-01 | GSE161901 | GEO

Single cell RNA-seq reveals developmental plasticity with coexisting oncogenic states and immune evasion programs in ETP-ALL [Patients_TALLs_scRNA-seq]

Project description:Lineage plasticity and stemness have been invoked as the cause of therapy resistance in cancer, as these flexible states allow cancer cells to de-differentiate and alter their dependencies. We investigated such resistance mechanisms in relapsed / refractory early T-cell progenitor acute lymphoblastic leukemia carrying activating NOTCH1 mutations, by full-length single cell RNA sequencing of malignant and microenvironmental cells. We identified two highly distinct stem-like states that critically differ in their cell-cycle and oncogenic signaling. Fast-cycling stem-like leukemia cells demonstrate Notch activation and are effectively eliminated in patients by Notch inhibition, while slow cycling stem-like cells are Notch-independent but rather rely on PI3K signaling, likely explaining the poor efficacy of Notch inhibition in this disease. Remarkably, we find that both stem-like states can differentiate into a more mature leukemia state with prominent immune-modulatory functions, including high expression of the LGALS9 checkpoint molecule. These cells promote an immunosuppressive leukemia ecosystem with clonal accumulation of dysfunctional CD8+ T cells that express HAVCR2, the cognate receptor for LGALS9. Our study identifies complex interactions between signaling programs, cellular plasticity and immune programs that characterize T-ALL and illustrates the multi-dimensionality of tumor heterogeneity. In this scenario, combination therapies targeting diverse oncogenic states and the immune ecosystem appear most promising to successfully eliminate tumor cells that escape treatment through co-existing transcriptional programs.

2021-01-01 | GSE161895 | GEO

Single cell RNA-seq reveals developmental plasticity with coexisting oncogenic states and immune evasion programs in ETP-ALL [PDX_ETPs_scRNA-seq]

2021-01-01 | GSE161896 | GEO

Metabolic profiling of ETP-ALL

Project description:Metabolic profiling of ETP-ALL

| PRJNA692461 | ENA

Single Cell RNAseq profiles of thymic ETP populations

Project description:The single cell profiles of sorted ETP populations with cell hashing antibody barcoding from mouse thymus

2019-10-16 | GSE137165 | GEO

Nucleosome accessibility in CUTLL3 cell line treated with Vehicle or Pitavastatin and 3 ETP-ALL patients

Project description:Analysis of nucleosome accessibility in CUTLL3 ETP-ALL cells following treatment with Vehicle or Pitavastatin for 48 hours and ETP-ALL patients at diagnosis

2021-10-21 | GSE164931 | GEO

Analysis of global gene expression of a human T-ALL cell lines, comparing GATA3low ETP-ALL (i.e. PER-117) and "typical" T-ALL

Project description:Cell lines representing human T-ALL were analyzed to compare GATA3low ETP-ALL (i.e. PER-117) with "typical" T-ALL. Moreover, changes in global gene expression were assessed comparing GATA3low ETP-ALL (i.e. PER-117) and GATA3high ETP-ALL (i.e. Loucy) upon treatment with Decitabine, a hypomethylating agent. Analysis of 6 human cell lines representing "typical" T-ALL (BE13, Jurkat, Molt4, RPM18402) and ETP-ALL (Loucy, PER-117). Additionally, global gene expression was assessed before and after treatment of ETP-ALL cell lines with Decitabine

2016-02-26 | E-GEOD-78166 | biostudies-arrayexpress

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