LMO2 is critical for early metastatic events in breast cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA668290 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12800248_1.fastq.gz | Fastqsanger.gz | |||
| SRR12800248_2.fastq.gz | Fastqsanger.gz | |||
| SRR12800249_1.fastq.gz | Fastqsanger.gz | |||
| SRR12800249_2.fastq.gz | Fastqsanger.gz | |||
| SRR12800250_1.fastq.gz | Fastqsanger.gz |
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Project description:This SuperSeries is composed of the SubSeries listed below.
2023-10-08 | GSE159285 | GEO
Project description:Lmo2 is an oncogenic transcription factor that is a frequent target of chromosomal abnormalities in this T-cell acute lymphoblastic leukemia (T-ALL). In transgenic mouse models, overexpression of Lmo2 causes thymocyte self-renewal leading to T-cell leukemia with long latency. However, the requirement of Lmo2 for maintenance of overt leukemia is poorly understood. We found that Lyl1, a critical cofactor for Lmo2-induced leukemia, is frequently lost in cell lines derived from Lmo2-transgenic mice, raising the possibility that Lmo2 function is dispensable at this stage. To study this, we developed a Tetracycline-repressible knock-in mouse model (Vav-TRE-Lmo2), which expresses Lmo2 throughout the haematopoietic system. This led to specific effects on T-cell development and the development of T-cell leukemia with long latency, preceded by the presence of self-renewing T-cells in the thymus. Repression of Lmo2 overcame the Lmo2-induced thymocyte developmental block at the preleukemic stage and led to elimination of Lmo2-induced thymocyte self-renewal in vivo. In contrast, Lmo2 function was dispensable for the majority of overt Lmo2-induced T-cell leukemias as well as leukemia-derived cell lines, implying an evolution of oncogene addiction in the majority of T-cell leukemias. Lmo2-dependence in T-ALL was associated with an immature gene expression profile, but could not be predicted by immunophenotype or assessment of Notch pathway activation. Thus, Lmo2 can give rise to both Lmo2-depenent and –independent T-cell leukemias. The Vav-TRE-Lmo2 model should be useful to determine the molecular features associated with Lmo2-dependence, as well as the critical components of the Lmo2-induced self-renewal pathways in T-ALL.
2022-01-01 | GSE125674 | GEO
Project description:These are raw mass spectrometry data discussed in our paper: “The LMO2-LDB1-TAL1 complex regulates transcription networks in AML”, where we implicate this multisubunit complex as a key regulator of leukemia cell transcription. The key method was affinity purification followed by tandem mass spectrometry. The LDB1 and LMO2 proteins were FLAG tagged and encoding cDNAs were cloned into lentiviral expression vectors allowing transduction of leukemia cells. Protein purification and MS/MS are described below.
2026-02-09 | PXD068576 | Pride
Project description:To determine the requirement for Lyl1 in Lmo2-driven T-ALL, microarray data was perepared from sorted CD4-CD8 double negative thymocytes of wild-type, Lmo2 transgenic and Lmo2-transgenic, Lyl1 knockout mice.
2013-07-25 | GSE49164 | GEO
Project description:To determine the requirement for Lyl1 in Lmo2-driven T-ALL, microarray data was perepared from sorted CD4-CD8 double negative thymocytes of wild-type, Lmo2 transgenic and Lmo2-transgenic, Lyl1 knockout mice. Total RNA obtained from sorted CD4-CD8 double-negative thymocytes
2013-07-25 | E-GEOD-49164 | biostudies-arrayexpress
Project description:To identify the binding partner of LMO2 for explanation of STAT3 signal-related protein in human glioblastoma
2022-08-11 | PXD028254 | Pride
Project description:Relapsed acute myeloid leukemia (relAML) remains a clinical challenge. We have shown that epigenetic heterogeneity may contribute to transcriptional dysregulation and disease progression in AML, but the specific transcriptional programs have not been identified. To characterize relAML transcriptional landscapes, we analyzed molecular profiles from patient-matched diagnostic and relapse AML specimens. A subset of differentially expressed genes (DEGs) that were disparate in direction of expression change identified two patient subtypes, but were not associated with specific molecular events. We predicted transcriptional regulators (TRs) that might regulate the expression patterns observed. The expression patterns of the top TRs predicted for the disparate genes associated with clinical outcomes in independent AML patient cohorts. The top TRs predicted included members of the LMO2 multi-subunit complex (TAL1 and LDB1). LMO2/LDB1/TAL1 complex members were also identified as potential TRs of DEGs in a patient derived xenograft mouse model of relapse. Analysis of DepMap data identified LMO2-dependent cells with a subset highly expressing TAL1, suggesting coordinated regulation. TAL1 co-purified in immunoprecipitation for LMO2 and LDB1 followed by tandem mass spectrometry analysis in HEL and K562 cells. Loss of function experiments targeting LMO2/LDB1/TAL1 in AML cell lines associated with reduced cell growth, downregulation of cell cycle genes, and a negative association with gene expression patterns observed in relapsed patients with increased TAL1 expression. Data from primary AML specimens and functional analyses of AML cell lines supports an essential role for the LMO2/LDB1/TAL1 complex in relAML. Targeting the complex or downstream effectors could provide novel therapeutic considerations for relAML patients.
2026-02-24 | GSE309129 | GEO
Project description:Prolonged or enhanced expression of the proto-oncogene Lmo2 is associated with a severe form of T-cell Acute Lymphoblastic Leukemia (T-ALL), designated Early T-progenitor ALL (ETP-ALL), that is characterized by the aberrant self-renewal and subsequent oncogenic transformation of immature thymocytes. Recent data suggest that Lmo2 may exert these effects by functioning as component of a multi-subunit transcription complex that includes the ubiquitous adapter Ldb1 along with b-HLH and/or GATA family transcription factors. In this study, we investigated the importance of Ldb1 for Lmo2-induced T-ALL by conditional deletion of Ldb1 in thymocytes in a Lmo2 transgenic mouse model of T-ALL. Our results identify a critical requirement for Ldb1 in the induction of thymocyte self-renewal, thymocyte radio-resistance and transition to T-ALL in Lmo2 transgenic mice. Ldb1 was also required for acquisition of the pre-leukemic ETP gene expression signature in immature Lmo2 transgenic thymocytes. Together, these results support a model where Lmo2-induced T-ALL results from failure to down-regulate Ldb/Lmo2 nucleated transcription complexes that normally function to enforce self-renewal in bone marrow hematopoietic progenitors
2020-03-19 | GSE129244 | GEO
Project description:Cellular plasticity in mammary epithelial cells enables dynamic cell state changes essential for normal developmental but can be hijacked by breast cancer cells to drive tumor progression. However, the molecular factors that maintain cellular plasticity through the regulation of a hybrid cell state (epithelial/mesenchymal) are not fully defined. As LMO2 has been previously shown to regulate metastasis, here we determined the role of LMO2 in the normal mammary epithelial cells . Using lineage tracing and knockout mouse models we find that Lmo2 lineage-traced cells persist long-term in the mammary gland, both in the luminal and basal layer but have limited proliferative potential. Lmo2 loss does not impact mammary gland development, but acute deletion decreases in vivo reconstitution. Moreover, LMO2 knockdown in mouse and human mammary epithelial cells (MECs) reduces organoid formation. We find that LMO2 maintains a hybrid cell state and LMO2 knockdown promotes mesenchymal differentiation. Transcriptional profiling of LMO2 knockdown cells reveals significant enrichment in the epithelial-mesenchymal transition (EMT) pathway and upregulation of MCAM, a negative regulator of regenerative capacity in the mammary gland . Altogether, we show that LMO2 plays a role in maintaining cellular plasticity in normal mammary epithelial cells, adding insight into the normal differentiation programs hijacked by cancer cells to drive tumor progression.
2026-02-19 | GSE298876 | GEO
Project description:Relapsed acute myeloid leukemia (relAML) remains a clinical challenge. We have shown that epigenetic heterogeneity may contribute to transcriptional dysregulation and disease progression in AML, but the specific transcriptional programs have not been identified. To characterize relAML transcriptional landscapes, we analyzed molecular profiles from patient-matched diagnostic and relapse AML specimens. A subset of differentially expressed genes (DEGs) that were disparate in direction of expression change identified two patient subtypes, but were not associated with specific molecular events. We predicted transcriptional regulators (TRs) that might regulate the expression patterns observed. The expression patterns of the top TRs predicted for the disparate genes associated with clinical outcomes in independent AML patient cohorts. The top TRs predicted included members of the LMO2 multi-subunit complex (TAL1 and LDB1). LMO2/LDB1/TAL1 complex members were also identified as potential TRs of DEGs in a patient derived xenograft mouse model of relapse. Analysis of DepMap data identified LMO2-dependent cells with a subset highly expressing TAL1, suggesting coordinated regulation. TAL1 co-purified in immunoprecipitation for LMO2 and LDB1 followed by tandem mass spectrometry analysis in HEL and K562 cells. Loss of function experiments targeting LMO2/LDB1/TAL1 in AML cell lines associated with reduced cell growth, downregulation of cell cycle genes, and a negative association with gene expression patterns observed in relapsed patients with increased TAL1 expression. Data from primary AML specimens and functional analyses of AML cell lines supports an essential role for the LMO2/LDB1/TAL1 complex in relAML. Targeting the complex or downstream effectors could provide novel therapeutic considerations for relAML patients.
2026-02-23 | GSE309225 | GEO