Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Leukemic progenitor compartment serves as a prognostic measure of cancer stemness in acute myeloid leukemic patients

ABSTRACT: Leukemic progenitor compartment serves as a prognostic measure of cancer stemness in acute myeloid leukemic patients

PROVIDER: PRJNA982842 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR24900057.fastq.gz	Fastqsanger.gz
	SRR24900058.fastq.gz	Fastqsanger.gz
	SRR24900059.fastq.gz	Fastqsanger.gz
	SRR24900060.fastq.gz	Fastqsanger.gz
	SRR24900061.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 18

Similar Datasets

Leukemic progenitor compartment serves as a prognostic measure of cancer stemness in acute myeloid leukemic patients

Project description:Single cell RNA sequencing of patient derived AML samples or xenografted human AML cells

2023-08-09 | GSE234743 | GEO

Leukemic progenitor compartment serves as a prognostic measure of cancer stemness in patients with acute myeloid leukemia.

Project description:We systematically investigate functional and molecular measures of stemness in patients with acute myeloid leukemia (AML) using a cohort of 121 individuals. We confirm that the presence of leukemic stem cells (LSCs) detected through in vivo xenograft transplantation is associated with poor survival. However, the measurement of leukemic progenitor cells (LPCs) through in vitro colony-forming assays provides an even stronger predictor of overall and event-free survival. LPCs not only capture patient-specific mutations but also retain serial re-plating ability, demonstrating their biological relevance. Notably, LPC content represents an independent prognostic factor in multivariate analyses including clinical guidelines of risk stratification. Our findings suggest that LPCs provide a robust functional measure of AML, enabling quantitative and rapid assessment of a wide range of patients. This highlights the potential of LPCs as a valuable prognostic factor in AML management.

| S-EPMC10394166 | biostudies-literature

Leukemic hematopoiesis

Project description:Leukemic hematopoiesis

| PRJNA881262 | ENA

Expression data from xenografted human leukemia cells comparing leukemic cells engrafted in the central nervous system (CNS) to leukemic cells derived from bone marrow (BM)

Project description:CNS leukemia is still the major obstacle in treating childhood acute lymphoblastic leukemia (ALL). We have used our NOD/SCID/huALL xenotransplantation model to identify molecular pathways leading to the infiltration of leukemic cells into the CNS compartment. We analysed gene expression differences of leukemic cells isolated from CNS and BM of CNS-positive samples using a microarray approach to detect expression differences between different infiltrated compartments.

2017-07-19 | GSE89710 | GEO

Ferritinophagy is a Druggable Vulnerability of Quiescent Leukemic Stem Cells in Acute Myeloid Leukemia

Project description:Acute myeloid leukemia (AML) remains a challenging hematological malignancy with poor prognosis and limited treatment options. Post-therapy relapse, particularly driven by leukemic stem cells (LSCs), contributes to therapeutic failure and adverse outcome. Here, we investigated the role of quiescence and its associated molecular mechanisms in AML pathogenesis and identified potential vulnerabilities for therapeutic intervention. We found that quiescent AML cells, enriched for LSC functions, exhibited a distinct gene set that served as a significant prognostic factor for poor outcomes in AML patients. Furthermore, quiescent cells displayed heightened autophagic activity, with a reliance on ferritinophagy, a selective form of autophagy mediated by Nuclear Receptor Coactivator 4 (NCOA4), for iron bioavailability. Inhibition of NCOA4 genetically or chemically showed potent anti-leukemic effects, particularly targeting the LSC compartment. These findings uncover that ferritinophagy inhibition may represent a promising therapeutic strategy for patients with AML.

2024-06-13 | PXD042796 | Pride

Targeting Mitochondrial Membrane Potential as A Generalized Strategy to Eradicate Leukemic Stem Cells

Project description:Heterogeneity in acute myeloid leukemias makes the development of effective therapies challenging. In the current study, we found that mitochondrial membrane potential (MMP) differs as a function of metabolism and stemness of leukemic cells. Mechanistically, MMP is regulated by mitochondrial translation, whose rate is sensitive to the availability of asparagine. Interestingly, this MMP-modulating mechanism is hijacked by leukemic cells, especially leukemic stem cells (LSCs), to elevated MMP to evade chemotherapy and thus depletion of asparagine by asparaginase chemo-sensitizes LSCs. To further evaluate the function of MMP-modulating mechanisms in disease development and drug resistance, we performed a targeted drug screen and identified Alexidine as a strong MMP-lowering agent via repressing mitochondrial translation. We revealed that Alexidine binds to cardiolipin to interfere with the inner membrane localization of mitochondrial ribosomes to inhibit mitochondrial translation. We demonstrated that Alexidine has anti-leukemic effect and is a potent chemo-sensitizer. Together, our study suggests that targeting MMP-modulating machineries is a promising approach to eradicate leukemic cells.

2024-09-01 | GSE266913 | GEO

Salmo trutta blood compartment

Project description:Salmo trutta blood compartment Metagenome

| PRJNA772886 | ENA

Cell-intrinsic Depletion of Aml1-ETO-positive Pre-leukemic HSCs by K-Ras Activating Mutation

Project description:Somatic mutations in acute myeloid leukemia (AML) are acquired sequentially and hierarchically. First, pre-leukemic mutations, such as t(8;21) that encodes AML1-ETO, are acquired within the hematopoietic stem cell (HSC) compartment, while signaling pathway mutations, including K-RAS activating mutations, are late events acquired during transformation of leukemic progenitor cells and rarely detectable in HSCs. This raises the possibility that signaling pathway mutations are detrimental to clonal expansion of pre-leukemic HSCs. To address this hypothesis we here used conditional genetics to introduce Aml1-ETO and K-RasG12D into murine HSCs, either individually or in combination. In the absence of activated Ras, Aml1-ETO expression conferred a competitive advantage to HSCs. However, activated K-Ras had a marked detrimental effect on Aml1-ETO expressing HSCs, leading to loss of both phenotypic and functional HSCs. Cell cycle analysis revealed a loss of quiescence in HSCs co-expressing Aml1-ETO and K-RasG12D, accompanied by an enrichment in E2F and Myc target gene expression and depletion of HSC self-renewal-associated gene expression. These findings provide a mechanistic basis for the observed absence of KRAS, and potentially other, signaling mutations in the pre-malignant HSC compartment.

2019-09-01 | GSE112024 | GEO

RBM17 Mediates Evasion of Pro-Leukemic Factors from Splicing-coupled NMD to Enforce Leukemic Stem Cell Maintenance

Project description:Acute myeloid leukemia (AML) patients suffer from chemo-resistance, high relapse frequency, and low overall survival rate, outcomes driven by leukemic stem cells (LSCs). Understanding the molecular mechanisms that support these primitive leukemic cells is crucial for developing effective AML therapeutics. In the present study, we demonstrate that upregulation of the splicing factor RBM17 preferentially marks and sustains the primitive compartment of AML. RBM17 expression is significantly higher in LSCs and its levels in human AML directly correlate with shortened survival in patients with the disease. RBM17 knockdown in primitive primary AML cells leads to myeloid differentiation and the impairment of their in vitro colony forming and in vivo engraftment capacities. To study the molecular mechanisms underlying the functional roles of RBM17 in AML, we performed global profiling of the RBM17-RNA interactome and proteome changes downstream of RBM17 knockdown. Through these integrative multi-omics analyses, we show that RBM17 repression leads to inclusion of poison exons and production of nonsense-mediated decay (NMD)-sensitive transcripts for pro-leukemic factors such as RBM39 and EZH2, along with the translation initiation factor EIF4A2. We further show that EIF4A2 expression is enriched in LSCs and inhibition of EIF4A2 impairs primary AML progenitor activity. Proteome analysis of AML cells after EIF4A2 knockdown demonstrate that EIF4A2 repression largely recapitulates the biological effect of RBM17 knockdown including the pronounced suppression of proteins involved in ribosome biogenesis. Overall, these results provide a rationale to target RBM17 and/or its downstream NMD-sensitive splicing substrates in primitive leukemic cells for AML treatment.

2022-04-26 | GSE180955 | GEO

Biomarkers to Measure Treatment Response for Alcohol Dependence

Project description:Biomarkers to Measure Treatment Response for Alcohol Dependence

| PRJNA971935 | ENA