Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

The effect of AML on platelets

ABSTRACT: Early diagnosis of acute myeloid leukemia (AML) in the pre-leukemic stage remains a clinical challenge, as pre-leukemic patients show no symptoms, lacking any known morphological or numerical abnormalities in blood cells. Here, we demonstrate that platelets with structurally abnormal mitochondria emerge at the pre-leukemic phase of AML, preceding detectable changes in blood cell counts or detection of leukemic blasts in blood. We visualized frozen-hydrated platelets from mice at different time points during AML development in situ using electron cryo-tomography (cryo-ET) and identified intracellular organelles through an unbiased semi-automatic process followed by quantitative measurement. A large proportion of platelets exhibited changes in the overall shape and depletion of organelles in AML. Notably, 23% of platelets in pre-leukemic cells exhibit abnormal, round mitochondria with unfolded cristae, accompanied by a significant drop in ATP levels and altered expression of metabolism-related gene signatures. Our study demonstrates that detectable structural changes in pre-leukemic platelets may serve as a biomarker for the early diagnosis of AML.

ORGANISM(S): Mus musculus

PROVIDER: GSE189844 | GEO | 2022/02/08

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Gene expression profiles associated with pediatric relapsed AML

Project description:In high income countries 90% of the patients achieve complete remission after induction chemotherapy. However, 30-40% of these patients suffer from relapse. These patients face a dismal prognosis, as the majority (>60%) of relapsed patients die within 5 years. As a result, outcome for pediatric acute myeloid leukemia (AML) patients remains poor and has stabilized over the past 15 years. To prevent or better treat relapse of AML is the best option to improve outcome. Despite patient specific differences, most patients do respond to initial therapy. This suggests that at relapse, mechanisms are active that cause the altered response to chemotherapy. Detailed understanding of mechanisms that cause relapse remain largely elusive. To gain insight in the molecular pathways that characterize relapsed AML, we performed genome wide gene expression profiling on paired initial diagnosis and relapsed AML samples of 23 pediatric AML patients. We used pathway analysis to find which molecular pathways are involved in altered gene expression between diagnosis and relapse samples of individual AML patients. 23 paired diagnosis and relapse bone marrow or peripheral blood samples were collected and cryo-preserved. They were later thawed and processed for hybridization to Affymetrix U133 Plus 2.0 arrays.

2015-05-07 | E-GEOD-52891 | biostudies-arrayexpress

Genotyping analysis of AML samples at diagnosis and relapse after Hematopoietic Stem Cell Transplantation (HSCT)

Project description:Genotype profiling of Acute Myeloid Leukemia samples. This dataset includes patients with diagnosis of de novo or secondary AML who experienced non-HLA loss disease relapse after allo-HCT, and for whom paired pre- and post-transplant viable leukemic samples were available.

2019-01-30 | E-MTAB-7631 | biostudies-arrayexpress

Transcriptome analysis of AML samples at diagnosis and relapse after Hematopoietic Stem Cell Transplantation (HSCT)

Project description:Transcriptome profiling of Acute Myeloid Leukemia samples. This dataset includes patients with diagnosis of de novo or secondary AML who experienced non-HLA loss disease relapse after allo-HCT, and for whom paired pre- and post-transplant viable leukemic samples were available.

2019-01-31 | E-MTAB-7628 | biostudies-arrayexpress

Transcriptome analysis of AML samples at diagnosis and relapse after Hematopoietic Stem Cell Transplantation (HSCT)

2019-01-29 | E-MTAB-7456 | biostudies-arrayexpress

Transcriptome analysis of AML samples at diagnosis and relapse after Hematopoietic Stem Cell Transplantation (HSCT)

2019-01-31 | E-MTAB-7630 | biostudies-arrayexpress

Transcription profiling of human pediatric acute myeloid leukemia samples

Project description:This series represents leukemic samples obtained from pediatric AML patients at diagnosis and control normal bone marrow samples.

2007-08-25 | E-GEOD-2191 | biostudies-arrayexpress

Leukemic initiation in Jam-C-deficient HSPC reveals AP-1/TNF- gene expression signature as a biomarker for AML

Project description:The leukemic stem cell score 17 (LSC-17) based on stemness gene expression signature is recognized as indicator of poor disease outcome in acute myeloid leukemia (AML). However, our understanding of the relationships between LSC and pre-leukemic cells is still incomplete. In particular, it is not known whether “niche-anchoring” of pre-leukemic cell affects disease evolution. To address this issue, we conditionally inactivated the adhesion molecule Jam-C expressed by haematopoietic stem cells (HSC) and LSC in an inducible iMLL-AF9-driven AML mouse model. Deletion of Jam-C in HSC before activation of the leukemia-initiating iMLL-AF9 fusion resulted in a shift from long term (LT-HSC) to short term-HSC (ST-HSC) expansion, suggesting that transcriptional programs of leukemic HSC were altered. RNA sequencing performed on leukemic HSC and GMP isolated from diseased mice revealed that genes upregulated in Jam-C-deficient animals belonged to Activation Protein-1 (AP-1) and TNF-/NFB signalling pathways. Using three publicly available datasets of AML gene expression, we further showed that human orthologs of dysregulated genes belonged to a gene regulon distinct from the LSC-17 signature. A prognosis 14-genes score from the AP-1/TNF-/NFB gene expression signature was established and called ATIC for “AP-1/TNF- initiating cell”. ATIC was independent of the LSC-17 score and improved the stratification of AML patients obtained with the LSC-17 score suggesting that the ATIC score reflected the presence of ST-HSC-initiating AML cells at diagnosis. Collectively we provide a novel tool for understanding AML disease heterogeneity through the identification of specific transcriptional programs for leukemic stem and progenitor cells.

2024-07-01 | GSE235693 | GEO

pediatric AML and normal bone marrow

Project description:This series represents leukemic samples obtained from pediatric AML patients at diagnosis and control normal bone marrow samples. Keywords: other

2005-01-28 | GSE2191 | GEO

Ribosome biogenesis factors are post-transcriptionally depleted in NPM1-mutant acute myeloid leukemia and can be targeted therapeutically

Project description:Mutations in the NPM1 gene are found in more than 30% of acute myeloid leukemia (AML) cases. The mutations disrupt a nucleolar localization signal (NoLS) and create a novel nuclear export signal (NES), leading to cytoplasmic displacement of the protein (NPM1c). NPM1c mutations prime hematopoietic progenitors to leukemic transformation, but their precise molecular consequences remain elusive. Here, we first examine the effects of isolated NPM1c mutations on the global proteome of pre-leukemic hematopoietic stem and progenitor cells (HSPCs) using conditional knock-in Npm1cA/+ mice. We discovered that many proteins involved in ribosome biogenesis are significantly depleted in these HSPCs, but also importantly in human NPM1-mutant AMLs. In line with this, we found that pre-leukemic Npm1cA/+ HSPCs display higher sensitivity to RNA pol I inhibitors, including Actinomycin D (ActD), compared to Npm1+/+ cells. Combination treatment with ActD and Venetoclax inhibited the growth and colony forming ability of pre-leukemic and leukemic NPM1c+ cells and low-dose ActD treatment was able to re-sensitize resistant NPM1c+ cells to Venetoclax. Furthermore, using data from CRISPR drop-out screens, we identified and validated TSR3, a 40S ribosomal maturation factor whose knock-out preferentially inhibited the proliferation of NPM1c+ AML cells by activating a p53-dependent apoptotic response. Similarly to low-dose ActD treatment, TSR3 depletion could partially restore sensitivity to Venetoclax in therapy-resistant NPM1c+ AML models.

2025-05-27 | PXD053249 | Pride