Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Long circulating RNAs identified as biomarker candidates for risk stratification in childhood acute lymphoblastic leukemia

ABSTRACT: Analysis of tumoral RNA is essential for childhood acute lymphoblastic leukemia (ALL) diagnosis and prognosis to detect mutations, cryptic fusions and gene expression patterns. Small vesicles circulating in the blood, such as exosomes carry nucleic acids that might be involved in cancer formation and progression, thus presenting a potential for discovery of non-invasive biomarker for diagnosis and monitoring. Here we report the identification of 47 circulating exosome-encapsulated RNA transcripts (30 mRNAs, 5 lncRNAs, 9 circRNAs and 3 pseudogenes) constituting putative biomarker in 2 molecular subgroups of childhood ALL patients. Exosomes were purified from peripheral blood collected at diagnosis from 10 patients positive for the ETV6-RUNX1 and TCF3-PBX1 fusions as well as from conditioned culture medium (CCM) of their representative cell models. Long transcriptome profiling via total RNA sequencing, supported by the implementation of a novel data analysis pipeline confirmed the presence of mRNAs, fusion transcripts, long non-coding and circular RNAs in exosomes. Differential expression analysis comparing tumoral and exosomal RNA revealed 2 transcripts enriched in both leukemic subtypes while 38 were exclusively enriched in ETV6-RUNX1+ patients and 7 were exclusively enriched in TCF3-PBX1+ patients. These are the first results highlighting specific enrichment of long RNA transcripts in exosomes among two distinct ALL subtypes, suggesting the need for investigation of larger cohorts to identify and validate novel circulating biomarkers.

ORGANISM(S): Homo sapiens

PROVIDER: GSE245139 | GEO | 2025/04/30

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Pilot-study for a novel universal tool for detection of oncogenic fusion transcripts

Project description:A novel oligonucleotide microarray design is described whereby one can screen for all known oncogenic fusion transcripts by one microarray hybridization. Measurements of chimeric transcript junctions are combined with exon-wise measurements of individual fusion partners. Keywords: Nimblegen custom-design The pilot data included a design with 68,861 oligonucleotide probes covering all combinations of chimeric exon-exon junctions from 275 pairs of fusion genes, as well as sets of oligos internal to all the exons of the fusion partners. Proof of principle was demonstrated by detection of known fusion genes (such as TCF3:PBX1, ETV6:RUNX1, and TMPRSS2:ERG) from six positive controls consisting of leukemia cell lines and prostate cancer biopsies.

2010-05-06 | E-GEOD-14435 | biostudies-arrayexpress

Proteomic analysis of patient-derived xenograft samples from children with B-cell acute lymphoblastic leukemia harboring TCF3::PBX1 and TCF3::HLF translocations

Project description:Despite improved 5-year overall survival rates in B-cell acute lymphoblastic leukemia (B-ALL) due to therapy escalation, effective treatments for relapsed and treatment-resistant disease, especially in specific subtypes like those with TCF3 (formerly E2A) fusions, remain scarce. TCF3, a key regulator of B-cell development, is implicated in various chromosomal translocations linked to lymphoid malignancies, such as TCF3::PBX1 fusion (5% of pediatric B-ALL) and TCF3::HLF fusion (~0.5% of pediatric B-ALL). Current omics research predominantly relies on transcriptomics, but it's increasingly recognized that this may not adequately reflect protein expression, the main targets of drugs and functional entities in biological processes. This study comprehensively analyzed proteomic landscapes of TCF3::HLF+ (n=6) and TCF3::PBX1+ (n=5) B-ALL using primary patient-derived xenografts (PDX), liquid chromatography tandem mass spectrometry, and data-dependent acquisition.

2024-07-05 | PXD053677 | Pride

INTEGRATED MULTI-OMICS ANALYSIS OF PBX1 IN MOUSE ADULT NEURAL STEMAND PROGENITOR CELLS IDENTIFIES A TRANSCRIPTIONAL MODULE WITH RELEVANCE TO LEUKEMOGENESIS

Project description:Developmental transcription factors act in networks, but how these networks achieve cell- and tissue specificity is still poorly understood. We here explored pre-B-cell leukemia homeobox 1 (PBX1) in adult neurogenesis combining genomic, transcriptomic, and proteomic approaches. ChIP-Seq analysis uncovered PBX1 binding to a wide range of different genes. Integration of PBX1 ChIP-seq with ATAC-seq data predicted interaction partners, which were subsequently validated by mass-spectrometry. Spatial transcriptomics revealed distinct temporal expression dynamics of Pbx1 and interacting factors. Among these were class I bHLH proteins TCF3, TCF4 and TCF12. RNA-seq upon Pbx1, Tcf3 and Tcf4 knockdown identified proliferation and differentiation associated genes as shared targets. Neuronal differentiation was reduced upon depletion of either factor, suggesting functional cooperation between PBX1 and TCF3/4. Notably, while physiological PBX1-TCF interactions have not yet been described, chromosomal translocation resulting in genomic TCF3::PBX1 fusion characterizes a subtype of acute lymphoblastic leukemia. Introducing Pbx1 into Nalm6 cells, a pre B-cell line expressing TCF3 but lacking PBX1, upregulated leukemogenic genes including BLK and NOTCH3, arguing that functional PBX1-TCF cooperation likely extends to hematopoietic contexts. Our study hence uncovers a PBX1-TCF module orchestrating the balance between progenitor cell proliferation and differentiation in adult neurogenesis with implications for leukemia etiology.

2024-09-16 | PXD048222 | Pride

Epigenomic mapping in B-cell acute lymphoblastic leukemia identifies transcriptional regulators and noncoding variants promoting distinct chromatin architectures [Hi-C]

Project description:Acute lymphoblastic leukemia (ALL) is the most common malignancy in pediatric patients and represents about a quarter of all pediatric malignancies. Past work has characterized B-cell lineage ALL (B-ALL) into molecular subtypes spanning a range of aberrant chromosomal rearrangements and oncogene chimeric fusions driving malignancy. While transcriptional and DNA methylome profiling of these subtypes has been extensively examined, the accompanying chromatin landscape and corresponding gene regulatory repertoire are not well characterized for many B-ALL subtypes. To better profile the B-ALL epigenome and gene regulatory networks we examined chromatin accessibility of 10 distinct molecular subtypes (BCR-ABL1, DUX4/ERG, ETV6-RUNX1, Hyperdiploid, Low hypodiploid, KMT2A-rearranged, Ph-like, PAX5-altered, TCF3-PBX1, ZNF384-rearranged and B-other) using 156 primary patient samples from across the United States with assay for transposase-accessible chromatin and high-throughput sequencing (ATAC-seq). In complement to ATAC-seq a subset of cell line and patient samples were profiled using promoter capture Hi-C to better define gene regulatory network connections.

2023-10-17 | GSE245222 | GEO

Clinicopathological features and prognostic value of SOX11 in childhood acute lymphoblastic leukemia

Project description:Acute lymphoblastic leukemia is marked by aberrant transcriptional features that alter cell differentiation, self-renewal, and proliferative features. We sought to identify the transcription factors exhibiting altered and subtype-specific expression patterns in B-ALL and report here that SOX11, a developmental and neuronal transcription factor, is aberrantly expressed in the ETV6-RUNX1 and TCF3-PBX1 subtypes of acute B-cell leukemias. We show that a high expression of SOX11 leads to alterations of gene expression that are typically associated with cell adhesion, migration, and differentiation. A high expression is associated with DNA hypomethylation at the SOX11 locus and a favorable outcome. The results indicate that SOX11 expression marks a group of patients with good outcomes and thereby prompts further study of its use as a biomarker.

2018-12-18 | GSE123943 | GEO

Self-Enforcing Feedback Activation between BCL6 and Pre-B Cell Receptor Signaling Defines a Distinct Subtype of Acute Lymphoblastic Leukemia

Project description:BCL6fl/fl mouse bone marrow pre-B cells were transduced with an TCF3-PBX1 vector. The TCF3-PBX1 transduced BCL6fl/fl pre-B cells were then transduced with an empty vector (EV), or a Cre vector for Cre-mediated BCL6 deletion. Effect of BCL6 deletion in the TCF3-PBX1 pre-B cells were studied by Affymetrix GeneChip Mouse Genome 430 2.0 Arrays.

2015-02-08 | GSE59332 | GEO

ATAC-seq of V-SVZ derived aNS cells

Project description:Developmental transcription factors act in networks, but how these networks achieve cell- and tissue specificity is still poorly understood. Here we explored pre-B cell leukemia homeobox 1 (PBX1) in adult neurogenesis combining genomic, transcriptomic, and proteomic approaches. ChIP-Seq analysis uncovered PBX1 binding to a wide range of different sites. Integration of PBX1 ChIP-seq with ATAC-seq data predicted interaction partners, which were subsequently validated by mass spectrometry. Spatial transcriptomics revealed distinct temporal expression dynamics of Pbx1 and interacting factors. Among these were class I bHLH proteins TCF3, TCF4 and TCF12. RNA-seq upon Pbx1, Tcf3 and Tcf4 knockdown identified proliferation- and differentiation associated genes as shared targets. Neuronal differentiation was reduced upon depletion of either factor, suggesting functional cooperation between PBX1 and TCF3/4. Notably, while physiological PBX1-TCF interactions have not yet been described, chromosomal translocation resulting in genomic TCF3::PBX1 fusion characterizes a subtype of acute lymphoblastic leukemia. Introducing Pbx1 into Nalm6 cells, a pre-B cell line expressing TCF3 but lacking PBX1, upregulated leukemogenic genes including BLK and NOTCH3, arguing that functional PBX1-TCF cooperation likely extends to hematopoietic contexts. Our study hence uncovers a PBX1-TCF module orchestrating the balance between progenitor cell proliferation and differentiation in adult neurogenesis with implications for leukemia etiology.

2024-09-16 | GSE248756 | GEO

RNA-seq of V-SZV derived aNS cells with siRNA mediated depletion of Pbx1, Tcf3 and Tcf4

2024-09-16 | GSE248755 | GEO

Chronic active pre-B cell receptor signaling drives BCL6 expression and represents a therapeutic target in a distinct subtype of acute lymphoblastic leukemia

2015-02-08 | E-GEOD-59332 | biostudies-arrayexpress

Self-enforcing Feedback Activation between BCL6 and Pre-B Cell Receptor Signaling Defines a Distinct Subtype of Acute Lymphoblastic Leukemia

Project description:We used ChIPseq in primary pre-B acute lymphomablastic leukemia (ALL) cells to identify target genes of the oncogenes TCF3-PBX1 and BCL6 that are involved in leukemogenesis of TCF3-PBX1 pre-B ALL. ChIP-seq using E2A (TCF3), PBX1, p300 and BCL6 antibodies in ICN12 cells (primary pre-B acute lymphomablastic leukemia)

2015-02-08 | E-GEOD-59538 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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