Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA291952 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Hematopoietic differentiation is required for initiation of acute myeloid leukemia [ATAC-seq]
| PRJNA291951 | ENA
Project description:Data for the manuscript Casirati et al. "Epitope Editing of Hematopoietic Stem Cells Enables Adoptive Immunotherapies for Acute Myeloid Leukemia"
2023-06-26 | MSV000092272 | MassIVE
Project description:Ezh2 augments leukemogenecity by reinforcing differentiation block in acute myeloid leukemia.
| PRJDB2048 | ENA
Project description:Ezh2 augments leukemogenecity by reinforcing differentiation block in acute myeloid leukemia.
| PRJDB2389 | ENA
Project description:Ezh2 augments leukemogenecity by reinforcing differentiation block in acute myeloid leukemia.
| PRJDB2603 | ENA
Project description:The hematopoietic system is maintained throughout life by hematopoietic stem cells that are capable of differentiation to all hematopoietic lineages. An intimate balance between self-renewal, differentiation, and quiescence is required to maintain hematopoiesis. Disruption of this balance can result in hematopoietic malignancy, including acute myeloid leukemia (AML). FBXO9, from the F-box ubiquitin E3 ligases, is down-regulated in patients with AML compared to normal bone marrow. FBXO9 is a substrate recognition component of the Skp1-Cullin-F-box (SCF)-type E3 ligase complex. FBXO9 is highly expressed in hematopoietic stem and progenitor populations, which contain the tumor-initiating population in AML. In AML patients, decrease in FBXO9 expression is most pronounced in patients with the inversion of chromosome 16 (Inv(16)), a rearrangement that generates the transcription factor fusion gene, CBFB-MYH11. To study FBXO9 in malignant hematopoiesis, we generated a conditional knockout mouse model using a novel CRISPR/Cas9 strategy. Our data shows that deletion of Fbxo9 in mice expressing Cbfb-MYH11 leads to markedly accelerated and aggressive leukemia development. In addition, we find loss of FBXO9 leads to increased proteasome expression and tumors are more sensitive to bortezomib suggesting that FBXO9 expression may predict patient response to bortezomib treatment.
2019-11-27 | PXD014387 | Pride
Project description:Leukemia initiating cells (LICs) of acute myeloid leukemia (AML) may arise from self-renewing hematopoietic stem cells (HSCs) and from committed progenitors. However, it remains unclear how leukemia-associated oncogenes instruct LIC formation from cells of different origins and if differentiation along the normal hematopoietic hierarchy is involved. Here, using murine models with the driver mutations MLL-AF9 or MOZ-TIF2, we found that regardless of the transformed cell types, myelomonocytic differentiation to the granulocyte macrophage progenitor (GMP) stage is critical for LIC generation. Blocking myeloid differentiation through disrupting the lineage-restricted transcription factor C/EBPa eliminates GMPs, blocks normal granulopoiesis, and prevents AML development. In contrast, restoring myeloid differentiation through inflammatory cytokines “rescues” AML transformation. Our findings identify myeloid differentiation as a critical step in LIC formation and AML development, thus guiding new therapeutic approaches. Primary KSL, CMP, and GMP cells from wildtype controls and C/Ebpa knockouts were used for RNA extraction and hybridization on Affymetrix microarrays. We also compared the microarray samples of leukemic granulocyte macrophage progenitor compartments (L-GMPs) from MLL-AF9 transformed control or cytokine rescued C/EBPa KO leukemic mouse bone marrow and their secondary recipients with those non-Leukemia KSLs and CMPs from MLL-AF9 transduecd KO recipients with no leukemia development.
2015-08-04 | E-GEOD-71687 | biostudies-arrayexpress
Project description:Leukemia initiating cells (LICs) of acute myeloid leukemia (AML) may arise from self-renewing hematopoietic stem cells (HSCs) and from committed progenitors. However, it remains unclear how leukemia-associated oncogenes instruct LIC formation from cells of different origins and if differentiation along the normal hematopoietic hierarchy is involved. Here, using murine models with the driver mutations MLL-AF9 or MOZ-TIF2, we found that regardless of the transformed cell types, myelomonocytic differentiation to the granulocyte macrophage progenitor (GMP) stage is critical for LIC generation. Blocking myeloid differentiation through disrupting the lineage-restricted transcription factor C/EBPa eliminates GMPs, blocks normal granulopoiesis, and prevents AML development. In contrast, restoring myeloid differentiation through inflammatory cytokines “rescues” AML transformation. Our findings identify myeloid differentiation as a critical step in LIC formation and AML development, thus guiding new therapeutic approaches. Primary KSL, CMP, and GMP cells from wildtype controls and C/Ebpa knockouts were used for RNA extraction and hybridization on Affymetrix microarrays. We also compared the microarray samples of leukemic granulocyte macrophage progenitor compartments (L-GMPs) from MLL-AF9 transformed control or cytokine rescued C/EBPa KO leukemic mouse bone marrow and their secondary recipients with those non-Leukemia KSLs and CMPs from MLL-AF9 transduecd KO recipients with no leukemia development.
2014-09-17 | E-GEOD-61468 | biostudies-arrayexpress
Project description:Leukemia initiating cells (LICs) of acute myeloid leukemia (AML) may arise from self-renewing hematopoietic stem cells (HSCs) and from committed progenitors. However, it remains unclear how leukemia-associated oncogenes instruct LIC formation from cells of different origins and if differentiation along the normal hematopoietic hierarchy is involved. Here, using murine models with the driver mutations MLL-AF9 or MOZ-TIF2, we found that regardless of the transformed cell types, myelomonocytic differentiation to the granulocyte macrophage progenitor (GMP) stage is critical for LIC generation. Blocking myeloid differentiation through disrupting the lineage-restricted transcription factor C/EBPa eliminates GMPs, blocks normal granulopoiesis, and prevents AML development. In contrast, restoring myeloid differentiation through inflammatory cytokines “rescues” AML transformation. Our findings identify myeloid differentiation as a critical step in LIC formation and AML development, thus guiding new therapeutic approaches. Examination of chromatin accessibility in Cebpa knock-out and control conditions.
2015-08-04 | E-GEOD-71688 | biostudies-arrayexpress