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Dynamic evolution of TCF3-PBX1 leukemias at the single-cell level under chemotherapy pressure [scRNA-seq]

ABSTRACT: Dynamic evolution of TCF3-PBX1 leukemias at the single-cell level under chemotherapy pressure [scRNA-seq]

PROVIDER: PRJNA978615 | ENA |

REPOSITORIES: ENA

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Dynamic evolution of TCF3-PBX1 leukemias at the single-cell level under chemotherapy pressure

Project description:Dynamic evolution of TCF3-PBX1 leukemias at the single-cell level under chemotherapy pressure

| PRJNA978609 | ENA

Dynamic evolution of TCF3-PBX1 leukemias at the single-cell level under chemotherapy pressure [Bulk RNA-seq]

Project description:Dynamic evolution of TCF3-PBX1 leukemias at the single-cell level under chemotherapy pressure [Bulk RNA-seq]

| PRJNA978614 | ENA

Dynamic evolution of TCF3-PBX1 leukemias at the single-cell level under chemotherapy pressure [scRNA-seq]

Project description:We have developed a mouse model in order to characterize in vivo chemotherapy resistance depending on niche. Global transcriptomics and phospho-proteomics at the single-cell level elucidated novel mechanisms of chemotherapy resistance depending on microenvironment, which might be suitable for pharmacological therapies. Comparison of the transcriptional profile of GFP+-sorted E2A-PBX1/preBCR+ leukemia cells in different tissues (bone marrow, spinal cord, lymph nodes, spleen) and after treatment with conventional chemotherapies prednisolone, daunorubicin compared to control (DMSO).

2024-09-20 | GSE233940 | GEO

Dynamic evolution of TCF3-PBX1 leukemias at the single-cell level under chemotherapy pressure [Bulk RNA-seq]

2024-09-20 | GSE233937 | GEO

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

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

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

Dynamic evolution of TCF3-PBX1 leukemias at the single-cell level under chemotherapy pressure

Project description:This SuperSeries is composed of the SubSeries listed below.

2024-09-20 | GSE233941 | 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

Transcriptome profiling of human pre-B ALL cell line 697 upon PBX1 or TCF3 knockdown (RNA-seq)

Project description:RNA-seq was performed to observe the gene expression changes in 697 cells following shRNA-mediated knockdown of PBX Homeobox 1 (PBX1) or Transcription Factor 3 (TCF3/E2A), each with two shRNAs. Cells treated with scrambled control shRNA were used as controls.

2020-05-13 | E-MTAB-8179 | biostudies-arrayexpress

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