Ff80869a-354f-4e73-bcec-1ef2957a6304 - samples
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ABSTRACT:
PROVIDER: EGAD00001011057 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:Inflammation in the bone marrow (BM) microenvironment is a constitutive component of acute myeloid leukemia (AML) pathogenesis. Studies have demonstrated that leukemic blasts propagate acute inflammation in the AML niche. Our recent studies in a congenic AML model suggest residual healthy hematopoietic stem and progenitor cells (HSPCs) participate in the inflammatory crosstalk. However, the underlying mechanism that drives the inflammatory conversion of HSPCs remains unclear. Here, we ask whether AML-derived extracellular vesicles (EV-AML) can convert HSPCs into an inflammatory active state in vivo. Using EV-AML purified from inducible (i)MLL-AF9 AML blasts (AF9-EV-AML), we challenged healthy C57BL/6J mice with serial injections of AF9-EVAML and analyzed HSPCs transcriptome. We show that HSPC transcriptome corroborates the enrichment of inflammatory and innate immune responses in EVAML-challenged BM HSPCs compared to controls. Our findings suggest that AML converts HSPCs into an inflammatory hub via EVAML in the AML niche.
2024-04-24 | GSE239307 | GEO
Project description:Bone marrow inflammation has been linked to acute myeloid leukemia (AML) progression. Studies have demonstrated that leukemic blasts propagate acute inflammation in the AML niche, but the involvment of normal hematopoietic stem and progenitor cells (HSPCs) in the inflammatory crosstalk is not well understood. To better model compartmental inflammation in AML, we first established a highly penetrant, immunocompetent, fully congenic system. Using the monoblastic AML cell line C1498 (CD45.2+), we grafted non-condition C57BL/6J (CD45.1) mice, avoiding changes in BM niche function. We then fluoresence-activated cell sorting (FACS)-sorted residual normal HSPCs for single-cell RNA-sequencing analysis. We show that residual normal HSPCs from C1498-grafted mice expresses key inflammatory signature and are enriched in inflammatory signaling related pathways. Overall, we show that normal HSPCs engages in inflammatory signaling in AML niche.
2024-01-01 | GSE238091 | GEO
Project description:Mutation in the nucleophosmin (NPM1) gene is frequent in acute myeloid leukemia (AML). This mutation has remarkable prognostic significance and correlates with distinct biological features. Our data from the sample-paired microRNA (miRNA) and mRNA microarrays of de novo AML patients strongly indicated that miRNAâmRNA regulation (MMR) may be dynamic and can be modulated by NPM1 mutation. We identified 493 NPM1 mutation-modulated MMR pairs by a systematic framework, in which MMR was attenuated specifically in patients carrying NPM1 mutations. The involved miRNAs/mRNAs were associated with cancer and hematological diseases, as well as known functions of NPM1 mutation including cell death and cellular response to therapeutics. The NPM1 mutation modulation could be validated with three approaches, including two independent cohort datasets, a high-throughput dataset derived from cell line-based experiments, and two in vitro models. Our study provides novel biological insights into the role of NPM1 mutation as a modulator of MMR, based on which novel prognostic markers are derived in AML. Cryopreserved bone marrow cells were obtained from 109 de novo AML patients. Each sample was analyzed with Illumina HumanHT-12 V4.0 expression beadchip.
2017-05-03 | E-GEOD-68466 | biostudies-arrayexpress
Project description:Mutation in the nucleophosmin (NPM1) gene is frequent in acute myeloid leukemia (AML). This mutation has remarkable prognostic significance and correlates with distinct biological features. Our data from the sample-paired microRNA (miRNA) and mRNA microarrays of de novo AML patients strongly indicated that miRNAâmRNA regulation (MMR) may be dynamic and can be modulated by NPM1 mutation. We identified 493 NPM1 mutation-modulated MMR pairs by a systematic framework, in which MMR was attenuated specifically in patients carrying NPM1 mutations. The involved miRNAs/mRNAs were associated with cancer and hematological diseases, as well as known functions of NPM1 mutation including cell death and cellular response to therapeutics. The NPM1 mutation modulation could be validated with three approaches, including two independent cohort datasets, a high-throughput dataset derived from cell line-based experiments, and two in vitro models. Our study provides novel biological insights into the role of NPM1 mutation as a modulator of MMR, based on which novel prognostic markers are derived in AML. Cryopreserved bone marrow cells were obtained from 109 de novo AML patients. Each sample was analyzed with nCounter® Human miRNA Expression Array.
2017-05-03 | E-GEOD-68467 | biostudies-arrayexpress
Project description:Multilineage dysplasia (MLD) has no impact on biological, clinico-pathological and prognostic features of AML with mutated nucleophosmin (NPM1) NPM1-mutated AML is a provisional entity in the WHO-2008 classification of myeloid neoplasms. The significance of concomitant multilineage dysplasia (MLD) in NPM1-mutated AML is unclear. Thus, in the WHO-2008 classification, NPM1-mutated AML with MLD is classified as AML with myelodysplasia(MD)-related changes. We evaluated the MLD impact in 378 NPM1-mutated AML patients. MLD was found in about 25% cases. Except for a lower WBC and FLT3-ITD incidence in MLD+ group, no significant differences were observed in age, sex, cytogenetics and FLT3-TKD between NPM1-mutated AML with and without MLD. Notably, NPM1-mutated AML with/without MLD showed overlapping immunophenotype (CD34-negativity) and GEP (CD34 downregulation and HOX genes upregulation). Moreover, OS and EFS did not differ among NPM1-mutated AML patients, independently of whether they carried or not MLD, the NPM1-mutated/FLT3-ITD negative cases showing the better prognosis. Lack of MLD impact on survival was confirmed by multivariate analysis that highlighted FLT3-ITD as the most significant prognostic parameter in NPM1-mutated AML. Our findings indicate that NPM1 mutations rather than MLD dictate the distinctive features of NPM1-mutated AML. Thus, irrespective of MLD, NPM1-mutated AML should be considered as one disease entity clearly distinct from AML with MD-related changes. These findings have important diagnostic and prognostic implications in AML. All bone marrow samples were obtained from untreated patients at the time of diagnosis. Cells used for microarray analysis were collected from the purified fraction of mononuclear cells after Ficoll density centrifugation. 48 samples
2010-07-30 | E-GEOD-18018 | biostudies-arrayexpress
Project description:The nucleolar scaffold protein NPM1 acts as a multifunctional regulator of cellular homeostasis, genome integrity, and stress response. NPM1 mutations, known as NPM1c variants that promote its aberrant cytoplasmic localization, are the most frequent genetic alterations in acute myeloid leukemia (AML). A hallmark of AML cells is their dependency on elevated autophagic flux. In order to identify the proteome changes upon NPM1 and NPM1c overexpression, we performed TMT-labeled mass spectrometry analysis of whole cell lysates.
2023-10-28 | PXD045357 | Pride
Project description:The nucleolar scaffold protein NPM1 acts as a multifunctional regulator of cellular homeostasis, genome integrity, and stress response. NPM1 mutations, known as NPM1c variants that promote its aberrant cytoplasmic localization, are the most frequent genetic alterations in acute myeloid leukemia (AML). A hallmark of AML cells is their dependency on elevated autophagic flux. In order to identify the proteome changes upon NPM1 and NPM1c overexpression, we performed TMT-labeled mass spectrometry analysis of whole cell lysates.
2023-11-20 | PXD040193 | Pride
Project description:A comprehensive taxonomy of the predicted interactions between LEPR + stromal niches, HSPCs and adaptive/innate immune cells in the human NBM and AML
| EGAS00001007330 | EGA
Project description:Multilineage dysplasia (MLD) has no impact on biological, clinico-pathological and prognostic features of AML with mutated nucleophosmin (NPM1) NPM1-mutated AML is a provisional entity in the WHO-2008 classification of myeloid neoplasms. The significance of concomitant multilineage dysplasia (MLD) in NPM1-mutated AML is unclear. Thus, in the WHO-2008 classification, NPM1-mutated AML with MLD is classified as AML with myelodysplasia(MD)-related changes. We evaluated the MLD impact in 378 NPM1-mutated AML patients. MLD was found in about 25% cases. Except for a lower WBC and FLT3-ITD incidence in MLD+ group, no significant differences were observed in age, sex, cytogenetics and FLT3-TKD between NPM1-mutated AML with and without MLD. Notably, NPM1-mutated AML with/without MLD showed overlapping immunophenotype (CD34-negativity) and GEP (CD34 downregulation and HOX genes upregulation). Moreover, OS and EFS did not differ among NPM1-mutated AML patients, independently of whether they carried or not MLD, the NPM1-mutated/FLT3-ITD negative cases showing the better prognosis. Lack of MLD impact on survival was confirmed by multivariate analysis that highlighted FLT3-ITD as the most significant prognostic parameter in NPM1-mutated AML. Our findings indicate that NPM1 mutations rather than MLD dictate the distinctive features of NPM1-mutated AML. Thus, irrespective of MLD, NPM1-mutated AML should be considered as one disease entity clearly distinct from AML with MD-related changes. These findings have important diagnostic and prognostic implications in AML.
2010-07-01 | GSE18018 | GEO
Project description:Acute myeloid leukemia (AML) is an aggressive and heterogeneous clonal disorder of hematopoietic stem/progenitor cells (HSPCs). It is not well known how leukemia cells alter hematopoiesis promoting tumor growth and leukemic niche formation. In this study, we investigated how AML deregulates the hematopoietic process of HSPCs through the release of extracellular vesicles (EVs). First, we found that AML cells released a heterogeneous population of EVs (AML-EVs) containing microRNAs involved in AML pathogenesis. Notably AML-EVs were able to influence the fate of HSPCs modifying their transcriptome. In fact, a gene expression profile of AML-EV-treated HSPCs identified approximately 923 down and 630 up-regulated genes involved in hematopoiesis/differentiation, inflammatory cytokine production and cell movement. Indeed, most of the downregulated genes are targeted by AML-EV-derived miRNAs. Furthermore, we demonstrated that AML-EVs were able to affect HSPCs phenotype, modifying several biological functions, such as inhibiting cell differentiation and clonogenicity, activating inflammatory cytokine production and compromising cell movement. Indeed, a redistribution of HSPC populations was observed in AML-EV treated cells with a significant increase in the frequency of common myeloid progenitors and a reduction in granulocyte-macrophage progenitors and megakaryocyte-erythroid progenitors. This effect was accompanied by a reduction in HSPC colony formation. AML-EV treatment of HSPCs increased the levels of CCL3, IL1B and CSF2 cytokines, involved in the inflammatory process and in cell movement, and decreased CXCR4 expression associated with a reduction of SDF-1 mediated-migration. In conclusion, this study demonstrates the existence of a powerful communication between AML cells and HSPCs, mediated by EVs, which suppresses normal hematopoiesis and potentially contributes to create a leukemic niche favorable to neoplastic development.
2022-03-11 | GSE189492 | GEO