Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

CD8+ T cells expand stem and progenitor cells in favorable but not adverse risk acute myeloid leukemia

ABSTRACT: We performed a comprehensive transcriptomic profiling of BM derived leukemia stem cells (LSCs) and leukemia progenitor cells (LPCs) together with paired CD8+ T cells of AML patients from different molecular risk groups, as well as hematopoietic stem cells (HSCs) and progenitor cells (HPCs) with paired CD8+ T cells of controls. This analysis revealed that epigenetic alterations mainly via histone deacetylation reduced the expression of immune-related genes in bone marrow (BM)-infiltrating CD8+ in AML when compared to CD8+ T cells in normal BM and that silenced gene expression pattern correlated with an improved prognosis. Correlation network modeling indicated that CD8+ T cells regulate leukemia stem/progenitor cells (LSPCs) in favorable risk but not in adverse risk AML.

ORGANISM(S): Homo sapiens

PROVIDER: GSE117090 | GEO | 2019/04/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Expression data in bone marrow mesenchymal stromal cells derived from acute myeloid leukemia patients

Project description:Acute myeloid leukemia (AML) is a heterogeneous clonal disorder of hematopoietic stem/progenitor cells characterized by excessive proliferation and subsequent accumulation of immature myeloid blasts, leading to impaired hematopoiesis in the bone marrow (BM). The progression of AML is closely linked to the crosstalk between leukemic cells and the BM microenvironment, in particular the mesenchymal stromal cells (MSCs). We compared the mRNA expression profile of BM-MSCs from newly diagnosed AML patients (n=3), relapsed AML patients (n=3) and healthy donor controls (n=3)

2021-11-26 | GSE122917 | GEO

Jiao2018 - Feedback regulation in a stem cell model with acute myeloid leukaemia

Project description:This is a mathematical model describing the hematopoietic lineages with leukemia lineages, as controlled by end-product negative feedback inhibition. Variables include hematopoietic stem cells, progenitor cells, terminally differentiated HSCs, leukemia stem cells, and terminally differentiated leukemia stem cells.

2019-12-17 | BIOMD0000000898 | BioModels

Bulk RNA sequencing of Bone Marrow Endothelial Progenitor Cells from Patients with Myelodysplastic Syndromes

Project description:Myelodysplastic syndromes(MDS) are a group of heterogeneous disease. Emerging evidence has shown the bone marrow(BM) endothelial progenitor cells(EPCs) are also heterogeneity. To uncover the underlying mechanism of heterogeneous BM EPCs in different types of MDS patients. RNA sequencing(RNA-seq) analyses were performed to analyse BM EPCs at day 7 in culture from lower-risk MDS(N=3), higher-risk MDS(N=3), acute myloid leukemia(AML) patients(N=3) and healthy donors(HDs)(N=3). We analysed the hematopoiesis- and immune-related genes and pathways.

2022-04-06 | GSE197907 | GEO

AML1-ETO induced leukemia stem cell self-renewal depends on Plcg1

Project description:High-resolution proteomic analysis of acute myeloid leukemia (AML) stem cells identified phospholipase C- and Ca++-signaling pathways to be differentially regulated in AML1-ETO (AE) driven leukemia. Phospholipase C gamma 1 (Plcg1) could be identified as a direct target of the AE fusion. Genetic Plcg1 inactivation abrogated disease initiation by AE, reduced intracellular Ca++-release and inhibited AE-driven self-renewal programs. In AE-induced leukemia, Plcg1 deletion significantly reduced disease penetrance, number of leukemia stem cells and abrogated leukemia development in secondary recipient hosts. In human AE-positive leukemic cells inactivation of Plcg1 reduced colony formation and AML development in vivo. In contrast, Plcg1 was dispensable for maintenance of murine and human hematopoietic stem- and progenitor cells (HSPCs). Pharmacologic inhibition of Ca++-signaling downstream of Plcg1 resulted in impaired proliferation and self-renewal capacity in AE-driven AML. Thus, the Plcg1 pathway represents a novel specific vulnerability of AE-driven leukemia and poses an important new therapeutic target.

2022-01-12 | PXD011251 | Pride

PLCG1 is required for AML1-ETO leukemia stem cell self-renewal

Project description:In an effort to identify novel drugs targeting fusion-oncogene induced acute myeloid leukemia (AML), we performed high-resolution proteomic analysis. In AML1-ETO (AE) driven AML we uncovered a deregulation of phospholipase C (PLC) signaling. We identified PLCgamma 1 (PLCG1) as a specific target of the AE fusion protein which is induced after AE binding to intergenic regulatory DNA elements. Genetic inactivation of PLCG1 in murine and human AML inhibited AML1-ETO dependent self-renewal programs, leukemic proliferation, and leukemia maintenance in vivo. In contrast, PLCG1 was dispensable for normal hematopoietic stem- and progenitor cell function. These findings are extended to and confirmed by pharmacologic perturbation of Ca++-signaling in AML1-ETO AML cells, indicating that the PLCG1 pathway poses an important therapeutic target for AML1-ETO positive leukemic stem cells.

2021-11-04 | PXD026374 | Pride

Single-cell transcriptomes of CD8+ T cells from patients with HR-MDS and AML

Project description:Treatment with hypomethylating agents (HMA), and specifically azacitidine (AZA), is the standard of care for patients with higher-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) that are not eligible to receive intensive chemotherapy. Despite research efforts, it is not possible to predict response to treatment with HMA. In this study, we aimed to identify immune cell signatures in the bone marrow (BM) associated with treatment outcomes. By employing mass cytometry, we performed an in-depth immunophenotypic analysis in BM samples deriving from patients with myeloid neoplasms prior to treatment initiation. We identified an increased pre-treatment frequency of a CD8+ T cell subset, characterized as CD57+CXCR3+CCR7-CD45RA+, in patients with MDS and AML who did not respond to treatment with AZA, compared to responders. Furthermore, a baseline frequency of more than 29% of CD57+CXCR3+CD8+ T cells was correlated with poor overall survival. We further engaged scRNA-seq to assess the transcriptional profile of BM CD8+ T cells from treatment-naïve patients with MDS and AML, to identify molecular signatures in CD8+ T subpopulations associated with favorable outcomes. Response to treatment was positively associated with enrichment of IFN-mediated pathways coupled with enhanced cytotoxic signature, whereas enrichment of the TGF-β signaling pathway was observed in cell clusters from non-responders. Together, this study identified a specific CD57+CXCR3+ CD8+ T cell population with predictive value in patients with MDS and AML treated with AZA, and characterized molecular signatures in CD8+ T cells linked to cytokine signaling that were associated with treatment outcomes.

2024-01-12 | GSE250077 | GEO

Highly multiplexed proteomic assessment of the human bone marrow microenvironment reveals elevated levels of CCL23 in acute myeloid leukemia

Project description:Acute myeloid leukemia (AML) is a genetically heterogeneous disease that is characterized by abnormal clonal proliferation of myeloid progenitor cells found predominately within the bone marrow (BM) and blood. Recent studies suggest that genetic and phenotypic alterations in the BM microenvironment support leukemogenesis and allow leukemic cells to survive and evade chemotherapy-induced death. However, despite substantial evidence indicating the role of tumor-host interactions in AML pathogenesis, little is known about the complex microenvironment of the BM. To address this, we performed novel proteomic profiling of the non-cellular compartment of the BM microenvironment in AML patients (n=10) and age- and sex-matched healthy controls (n=10) using an aptamer-based, highly multiplexed, affinity proteomics platform (SOMAscan). We demonstrate that proteomic assessment of blood or RNA-sequencing of BM are suboptimal alternate screening strategies to determine the true proteomic composition of the extracellular compartment of the AML marrow microenvironment. Proteomic analysis showed 168 proteins significantly differed in abundance, with 91 proteins up-regulated and 77 proteins down-regulated in leukemic BM. A highly connected signaling network of cytokines and chemokines, including IL-8, was found to be the most prominent proteomic signature associated with AML in the BM microenvironment. We report the first description of significantly elevated levels of the myelosuppressive chemokine CCL23 (MPIF–1) in both AML and MDS patients and perform functional experiments supportive of a role in the suppression of normal hematopoiesis. This unique paired RNA-sequencing and proteomics dataset provides innovative mechanistic insights into AML and healthy aging and should serve as a useful public resource.

2020-02-03 | GSE138702 | GEO

IL-33–ST2 signaling promotes stemness in subtypes of myeloid leukemia cells through the Wnt and Notch pathways

Project description:Purpose: The goal was to compare transcriptome profile of FACS-purified bone marrow AML1/ETO positive LSPCs from AML patients treated with rhIL-33 or controls (untreated). Methods: The transcriptomic analysis of AML1/ETO positive LSPCs were assessed in biological replicates upon treatment treated rhIL-33 or controls using Illumina NextSeq 500. Results: We mapped around 30 million sequence reads per sample to the human genome (GRCh38 - hg38) and identified differentially expressed transcripts in FACS-purified bone marrow AML1/ETO positive LSPCs from AML patients treated with rhIL-33 or controls (untreated). Differentially expressed genes between LSPCs treated with rhIL-33 or controls, were identified with a fold change ≥1.5 and FDR p-value <0.05. Conclusions: Our study represents the first detailed RNA-seq analysis of FACS-purified bone marrow AML1/ETO positive LSPCs from AML patients treated with rhIL-33 or controls. Our results show that IL-33 treatment induces the regulation of metabolic process, cell cycle, regulation of NF-κΒ, MAPK and canonical Wnt signaling pathways, as well as the regulation of stem cell division and maintenance.

2023-08-28 | GSE190687 | GEO

C1Q labels a highly aggressive macrophage-like leukemia population indicating extramedullary infiltration and relapse

Project description:Extramedullary infiltration (EMI) is a concomitant manifestation indicating poor prognosis of acute myeloid leukemia (AML), yet the underlying mechanism remains poorly understood and therapeutic options are limited. Here, we employed single-cell RNA sequencing on bone marrow (BM) and EMI samples from an AML patient presenting pervasive leukemia cutis. A complement C1Q + macrophage-like leukemia subset which is enriched within cutis and existed in BM prior to EMI manifestations was identified and further verified in multiple AML patients. RNA-sequencing and quantitative proteomics profiling revealed adverse prognosis of patients bearing C1Q + population. C1Q expression endowed leukemia cells with tissue-infiltration ability which could establish prominent cutaneous or gastrointestinal EMI nodules in patient-derived xenograft (PDX) and CDX models. Fibroblasts attracted migration of the C1Q + leukemia cells through surface C1Q-gC1QR recognition and subsequent stimulation of MAFB-TGF-β signaling. Thus, C1Q orchestrates cancer infiltration pathways through communicating with fibroblasts and represents a compelling therapeutic target for EMI.

2022-08-03 | PXD035784 | iProX

Inflammatory conversion of normal hematopoietic stem and progenitor cells by acute myeloid leukemia derived extracellular vesicles in vivo

Project description:Inflammation in the bone marrow (BM) microenvironment is a constitutive component of acute myeloid leukemia (AML) pathogenesis. Studies have demonstrated that leukemic blasts propagate acute inflammation in the AML niche. Our recent studies in a congenic AML model suggest residual healthy hematopoietic stem and progenitor cells (HSPCs) participate in the inflammatory crosstalk. However, the underlying mechanism that drives the inflammatory conversion of HSPCs remains unclear. Here, we ask whether AML-derived extracellular vesicles (EV-AML) can convert HSPCs into an inflammatory active state in vivo. Using EV-AML purified from inducible (i)MLL-AF9 AML blasts (AF9-EV-AML), we challenged healthy C57BL/6J mice with serial injections of AF9-EVAML and analyzed HSPCs transcriptome. We show that HSPC transcriptome corroborates the enrichment of inflammatory and innate immune responses in EVAML-challenged BM HSPCs compared to controls. Our findings suggest that AML converts HSPCs into an inflammatory hub via EVAML in the AML niche.

2024-04-24 | GSE239307 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data