Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Ena-DATASET-FIMM-20-06-2016-14:40:19:517-22 - samples

ABSTRACT: Sequence data is from 4 samples from an adult patient with TCF3-PBX1 t(1;19)-positive acute lymphoblastic leukemia. Exome sequencing was performed on a skin biopsy (normal tissue control) and leukemic bone marrow biopsies taken at diagnosis and at two relapse time points. RNA-sequence data is from leukemic bone marrow from two relapse biopsies.

PROVIDER: EGAD00001002203 | EGA |

REPOSITORIES: EGA

ACCESS DATA

Json Xml

Publications

Idelalisib sensitivity and mechanisms of disease progression in relapsed TCF3-PBX1 acute lymphoblastic leukemia.

Eldfors S S Kuusanmäki H H Kontro M M Majumder M M MM Parsons A A Edgren H H Pemovska T T Kallioniemi O O Wennerberg K K Gökbuget N N Burmeister T T Porkka K K Heckman C A CA

Leukemia 20160727 1

TCF3-PBX1 (E2A-PBX1) is a recurrent gene fusion in B-cell precursor acute lymphoblastic leukemia (BCP-ALL), which is caused by the translocation t(1;19)(q23;p13). TCF3-PBX1 BCP-ALL patients typically benefit from chemotherapy; however, many relapse and subsequently develop resistant disease with few effective treatment options. Mechanisms driving disease progression and therapy resistance have not been studied in TCF3-PBX1 BCP-ALL. Here, we aimed to identify novel treatment options for TCF3-PBX1 ...[more]

PMID: 27461063

Similar Datasets

Chronic active pre-B cell receptor signaling drives BCL6 expression and represents a therapeutic target in 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. TCF3-PBX1 transduced BCL6fl/fl mice bone marrow pre-B cells were tranduced with an empty vector (EV) or a Cre vector for BCL6 deletion

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

2015-02-08 | GSE59332 | GEO

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

Exome and RNA sequencing of relapsed TCF3-PBX1 t(1;19) acute lymphoblastic leukemia

Project description:TCF3-PBX1 (E2A-PBX1) is a recurrent gene fusion in B-cell precursor lymphoblastic leukemia (BCP-ALL), which is caused by the translocation t(1;19)(q23;p13). TCF3-PBX1 BCP-ALL patients typically benefit from chemotherapy; however, many relapse and subsequently develop resistant disease with few effective treatment options. Mechanisms driving disease progression and therapy resistance have not been studied in TCF3-PBX1 BCP-ALL. Here, we aimed to identify novel treatment options for TCF3-PBX1 BCP-ALL by profiling leukemia cells from a relapsed patient, and determine molecular mechanisms underlying disease pathogenesis and progression. By drug sensitivity testing of leukemic blasts from the index patient, control samples and TCF3-PBX1 positive and negative BCP-ALL cell lines, we identified the phosphatidylinositide 3-kinase delta (p110δ) inhibitor idelalisib as an effective treatment for TCF3-PBX1 BCP-ALL. This was further supported by evidence showing TCF3-PBX1 directly regulates expression of PIK3CD, the gene encoding p110δ. Other somatic mutations to TP53 and MTOR, as well as aberrant expression of CXCR4, may influence additional drug sensitivities specific to the index patient and accompanied progression of the disease. Our results suggest that idelalisib is a promising treatment option for patients with TCF3-PBX1 BCP-ALL while other drugs could be useful depending on the genetic context of individual patients.

| EGAS00001001876 | EGA

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

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

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

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

2015-02-08 | GSE59538 | GEO

DNA and RNA Sequence of an Acute Lymphoblastic Leukemia

Project description:<p>We used massively parallel sequencing technology to profile the genomic DNA and RNA of tumor cells (leukemic bone marrow) and normal cells (skin biopsy) obtained from a single patient with Acute Lymphoblastic Leukemia (ALL), referred to throughout this study as 'ALL1'. Included in this study are samples obtained from a primary tumor, first relapse, second relapse and several intermediate timepoints. We identified somatic mutations present in each tumor by analysis of whole genome (WGS) and exome sequence data. Single nucleotide variants (SNVs) and small insertions and deletions were identified in both the exome and WGS data. Large copy number variations (CNVs) and structural variants (SVs) were identified in the WGS data. A custom capture reagent was designed to target most variants and used to generate deep validation sequence data. The expression status of all somatic variants was assessed by RNA-seq. The RNA-seq data was also used for gene expression analysis and gene fusion detection.</p>

| phs001066 | dbGaP

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