N-Myc overexpression leads to multiple types of acute leukemia in mice
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ABSTRACT:
PROVIDER: PRJNA610169 | ENA |
REPOSITORIES: ENA
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Project description:N-Myc overexpression leads to multiple types of acute leukemia in mice [WGS]
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Project description:N-Myc overexpression leads to multiple types of acute leukemia in mice [RNA-Seq]
| PRJNA610171 | ENA
Project description:The expression of the oncogene MYCN is upregulated in acute leukemia. However, the role of MYCN in leukemogenesis is poorly understood. We established multiple types of leukemia by retroviral overexpression of N-Myc in mice and studied the mechanism of leukemogenesis. Two types of hematopoietic stem cells and three types of hematopoietic progenitor cells highly purified from the bone marrow of adult C57BL/6 mice were transduced with N-Myc and transplanted into lethally irradiated mice. Acute leukemia developed from all these populations. Notably, not only B cell acute lymphoid leukemia, but also T cell acute lymphoid leukemia, acute myeloid leukemia, acute undifferentiated leukemia, and mixed phenotype acute leukemia developed, suggesting the multiple cells of origin, regardless types of leukemia. Moreover, leukemic stem cells were identified in Kit+Sca-1+Lin- bone marrow cells. RNA-seq data revealed the leukemia type-specific transcription profiles. Interestingly, acute undifferentiated leukemia appeared to be transcriptionally close to T cell acute lymphoid leukemia. Whole genome sequencing suggested that different types of leukemia arose associated with a large number of gene mutations induced by N-Myc overexpression but independent of retroviral integration sites. This study provides a new mouse model in which varying types of leukemia develop by only one oncogene.
2023-03-01 | GSE146331 | GEO
Project description:The expression of the oncogene MYCN is upregulated in acute leukemia. However, the role of MYCN in leukemogenesis is poorly understood. We established multiple types of leukemia by retroviral overexpression of N-Myc in mice and studied the mechanism of leukemogenesis. Two types of hematopoietic stem cells and three types of hematopoietic progenitor cells highly purified from the bone marrow of adult C57BL/6 mice were transduced with N-Myc and transplanted into lethally irradiated mice. Acute leukemia developed from all these populations. Notably, not only B cell acute lymphoid leukemia, but also T cell acute lymphoid leukemia, acute myeloid leukemia, acute undifferentiated leukemia, and mixed phenotype acute leukemia developed, suggesting the multiple cells of origin, regardless types of leukemia. Moreover, leukemic stem cells were identified in Kit+Sca-1+Lin- bone marrow cells. RNA-seq data revealed the leukemia type-specific transcription profiles. Interestingly, acute undifferentiated leukemia appeared to be transcriptionally close to T cell acute lymphoid leukemia. Whole genome sequencing suggested that different types of leukemia arose associated with a large number of gene mutations induced by N-Myc overexpression but independent of retroviral integration sites. This study provides a new mouse model in which varying types of leukemia develop by only one oncogene.
2023-03-01 | GSE146330 | GEO
Project description:The MYC oncogene encodes for the MYC protein and is frequently dysregulated across multiple cancer cell types, making it an attractive target for cancer therapy. MYC overexpression leads to MYC binding at active enhancers, resulting in a global transcriptional amplification of active genes. Since superenhancers are frequently dysregulated in cancer, we hypothesized that MYC preferentially invades into superenhancers and alters the cancer genome organization. To that end, we performed ChIP-seq, RNA-seq, 4C-seq and SIQHiC (Spike-in Quantitative Hi-C) on the U2OS osteosarcoma cell line with tetracycline-inducible MYC. MYC overexpression in U2OS cells modulated histone acetylation and increased MYC binding at superenhancers. SIQHiC analysis revealed increased global chromatin contact frequency, particularly at chromatin interactions connecting MYC binding sites at promoters and enhancers. Immunofluorescence staining showed that MYC molecules formed punctate foci at these transcriptionally active domains after MYC overexpression. These results demonstrate the accumulation of overexpressed MYC at promoter-enhancer hubs and suggest that MYC invades into enhancers through spatial proximity. At the same time, the increased protein-protein interactions may strengthen these chromatin interactions to increase chromatin contact frequency. CTCF siRNA knockdown in MYC overexpressed U2OS cells demonstrated that removal of architectural proteins can disperse MYC and abrogate the increase in chromatin contacts. By elucidating the chromatin landscape of MYC driven cancers, we can potentially target MYC associated chromatin interactions for cancer therapy.
2022-01-17 | GSE164777 | GEO
Project description:MYC overexpression leads to increased chromatin interactions at superenhancers and MYC binding sites
| PRJNA691927 | ENA
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-03-01 | GSE146333 | GEO
Project description:HeLa, ZBTB2-myc overexpression, 0.1% O2
| PRJNA928321 | ENA
Project description:To identify how MYC overexpression remodels the cell surface proteome in a cell autologous fashion and in different cell types, we investigated the impact of MYC overexpression on ~800 surface proteins in three isogenic model cell lines either of B-cell or prostate cell origin that were engineered to contain either high or low MYC.
2020-08-07 | MSV000085930 | MassIVE
Project description:DHX15 has been implicated in RNA splicing and ribosome biogenesis, primarily functioning as an RNA helicase. To systematically assess the cellular role of DHX15, we conducted proteomic analysis to investigate the landscape of DHX15 interactome, and identified MYC as a binding partner. DHX15 co-localizes with MYC in cells and directly interacts with MYC in vitro. Importantly, DHX15 contributes to MYC protein stability at the post-translational level and independent of its RNA binding capacity. Mechanistic investigation reveals that DHX15 interferes the interaction between MYC and FBXW7, thereby preventing MYC polyubiquitylation and proteasomal degradation. Consequently, abrogation of DHX15 drastically inhibits MYC-mediated transcriptional output. While DHX15 depletion blocks T-cell development and leukemia cell survival as we recently reported, overexpression of MYC significantly rescues the phenotypic defects. These findings shed new light on the essential role of DHX15 in mammalian cells and suggest that maintaining sufficient MYC expression is a significant contributor to DHX15-mediated cellular functions.
2024-01-26 | PXD046692 | Pride