Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B-cell Acute Lymphoblastic Leukemia Cell

SUBMITTER: Vanessa Masson

LAB HEAD: Damarys Loew

PROVIDER: PXD053677 | Pride | 2024-07-05

REPOSITORIES: Pride

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	Design.xlsx	Xlsx
	X1738FD.msf	Msf
	X1738FD.raw	Raw
	X1739FD.msf	Msf
	X1739FD.raw	Raw

Items per page:

1 - 5 of 23

Similar Datasets

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

Interactome of the TCF3-HLF fusion protein

Project description:Oncogenic chimeric transcription factors are central drivers in cancer. To understand how the TCF3-HLF fusion protein rewires the transcriptional landscape in t(17;19) positive leukemia, functional genetic and proteomic experiments were conducted. In this dataset, the protein-protein interactions of the endogenous TCF3-HLF complex were characterized by AP-MS.

2020-08-05 | PXD014992 | Pride

ChIP-chip by SNP array of a case of a patient with TCF3-HLF-positive BCP-ALL

Project description:The TCF3-HLF translocation is a very rare rearrangement in ALL that is associated with an extremely poor prognosis. The TCF3-HLF fusion gene in the described case resulted in the fusion of the homeobox-related gene of TCF3 to the leucine zipper domain of HLF. The TCF3-HLF fusion gene product acts as a transcriptional factor leading to the dedifferentiation of mature B lymphocytes into an immature state (lymphoid stem cells). This process initiates the formation of pre-leukaemic cells. Due to the rarity of this chromosomal aberration, only a few cases have been described in the literature. The advantage of this work is the presentation of an interesting case of clonal evolution of cancer cells and the cumulative implications (diagnostic and prognostic) of the patient’s genetic alterations.

2020-03-20 | GSE147280 | 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

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

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 | GSE248755 | GEO

ATAC-seq of V-SVZ derived aNS cells

2024-09-16 | GSE248756 | 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

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

GFP-CYYR1 interactome vs. GFP in HEK293 cells

Project description:Cell lysates from HEK293 cells individually transfected with GFP or GFP-CYYR1 were purified on GFP-Trap affinity resin and analyzed by quantitative label-free mass spectrometry. Experiments were performed in 5 biological replicates for each condition.

2024-07-25 | PXD050895 | Pride