Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RNA sequencing for AML patients with and without extramedullary infiltration

ABSTRACT: Extramedullary infiltration (EMI) is a concomitant manifestation indicating poor prognosis of acute myeloid leukemia (AML), yet the underlying mechanism remains poorly understood and therapeutic options are limited. Here, we employed single-cell RNA sequencing on bone marrow (BM) and EMI samples from an AML patient presenting pervasive leukemia cutis. A complement C1Q+ macrophage-like leukemia subset which is enriched within cutis and existed in BM prior to EMI manifestations was identified and further verified in multiple AML patients. RNA-sequencing and quantitative proteomics profiling revealed adverse prognosis of patients bearing C1Q+ population. C1Q expression endowed leukemia cells with tissue-infiltration ability which could establish prominent cutaneous or gastrointestinal EMI nodules in patient-derived xenograft (PDX) and CDX models. Fibroblasts attracted migration of the C1Q+ leukemia cells through surface C1Q-gC1QR recognition and subsequent stimulation of MAFB5 TGF-β signaling. Thus, C1Q orchestrates cancer infiltration pathways through communicating with fibroblasts and represents a compelling therapeutic target for EMI.

ORGANISM(S): Homo sapiens

PROVIDER: GSE213584 | GEO | 2023/04/07

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Shared Molecules

Only show the datasets with similarity scores above: 0.5

Threshold

0.5

Similar Datasets

C1Q labels a highly aggressive macrophage-like leukemia population indicating extramedullary infiltration and relapse

Project description:Extramedullary infiltration (EMI) is a concomitant manifestation indicating poor prognosis of acute myeloid leukemia (AML), yet the underlying mechanism remains poorly understood and therapeutic options are limited. Here, we employed single-cell RNA sequencing on bone marrow (BM) and EMI samples from an AML patient presenting pervasive leukemia cutis. A complement C1Q + macrophage-like leukemia subset which is enriched within cutis and existed in BM prior to EMI manifestations was identified and further verified in multiple AML patients. RNA-sequencing and quantitative proteomics profiling revealed adverse prognosis of patients bearing C1Q + population. C1Q expression endowed leukemia cells with tissue-infiltration ability which could establish prominent cutaneous or gastrointestinal EMI nodules in patient-derived xenograft (PDX) and CDX models. Fibroblasts attracted migration of the C1Q + leukemia cells through surface C1Q-gC1QR recognition and subsequent stimulation of MAFB-TGF-β signaling. Thus, C1Q orchestrates cancer infiltration pathways through communicating with fibroblasts and represents a compelling therapeutic target for EMI.

2022-08-03 | PXD035784 |

Expression data of circRNA from new diagnostic AML patients (with or without EMI) and healthy volunteers

Project description:CircRNA microarray was conducted to further explore the underlying circRNA expression alterations in extramedullary infiltration (EMI) of AML. 4 matched samples from EMI, non-EMI AML patients and healthy volunteers were selected. Mononuclear cells from 12 bone marrow samples were separated according to protocols. RNA was then extracted and hybridization for further microarray analysis.

2018-07-04 | GSE116617 | GEO

Expression data of whole genome from new diagnostic AML patients (with or without EMI) and healthy volunteers

Project description:Whole Genome microarray was conducted to further explore the underlying gene expression alterations in extramedullary infiltration (EMI) of AML. 4 matched samples from EMI, non-EMI AML patients and healthy volunteers were selected. Mononuclear cells from 12 bone marrow samples were separated according to protocols. RNA was then extracted and hybridization for further microarray analysis.

2018-07-04 | GSE116616 | GEO

CD8+ T cells expand stem and progenitor cells in favorable but not adverse risk acute myeloid leukemia

Project description:We performed a comprehensive transcriptomic profiling of BM derived leukemia stem cells (LSCs) and leukemia progenitor cells (LPCs) together with paired CD8+ T cells of AML patients from different molecular risk groups, as well as hematopoietic stem cells (HSCs) and progenitor cells (HPCs) with paired CD8+ T cells of controls. This analysis revealed that epigenetic alterations mainly via histone deacetylation reduced the expression of immune-related genes in bone marrow (BM)-infiltrating CD8+ in AML when compared to CD8+ T cells in normal BM and that silenced gene expression pattern correlated with an improved prognosis. Correlation network modeling indicated that CD8+ T cells regulate leukemia stem/progenitor cells (LSPCs) in favorable risk but not in adverse risk AML.

2019-04-04 | GSE117090 | GEO

RNA sequencing for AML patients with and without extramedullary infiltration

Project description:RNA sequencing for AML patients with and without extramedullary infiltration

| PRJNA881603 | ENA

mRAN expression profiles in mesenchymal progenitor cells freshly-sorted from Wild Type and Lama4-deficient mice

Project description:Bone marrow (BM) niche contributes to hematopoietic regeneration under stress like irradiation and leukemia. However, the mechanisms remain poorly defined. We here report that Lama4 deletion in mice results in reduction of mesenchymal progenitors (MPCs) and endothelial cells in BM. Following irradiation, Lama4-/- mice displayed impaired hematopoiesis recovery accompanied with dysregulation of BM niche factors like angiopoietin-1 and Tgfb1 in the MPCs. Post-transplantation of MLL-AF9 acute myeloid leukemia (AML) cells, we observed accelerated AML onset in Lama4-/- mice. Moreover, these Lama4-/- AML mice displayed faster relapse after therapeutic BM transplantation. Mechanistically, Lama4-/- niche promoted AML cell proliferation and chemoresistance to chemotherapy cytarabine by conferring AML greater antioxidant activity. Together, our study demonstrates that Lama4 is required to maintain hematopoietic niche integrity and to suppress AML progression and chemoresistance by restricting metabolic defense support to AML. Therefore, activating Lama4 signaling pathways may offer potential new therapeutic options for AML.

2022-02-16 | GSE167404 | GEO

Transcriptome analysis of C1q treated lung fibroblasts

Project description:Pulmonary fibrosis (PF) is a progressive fibrotic disease with a poor prognosis and suboptimal therapeutic options. The complement molecule C1q, which plays an important role in the phagocytic capacity of macrophages, has recently been reported to exacerbate several fibrosis-related diseases. On the other hand, there are still no reports in PF. Here, we analyzed the effect of C1q treatment on lung fibroblasts.

2024-03-31 | GSE184438 | GEO

VEXAS syndrome, myelodysplasia cutis and sweet syndrome skin lesions share a common transcriptomic profile led by interferon signaling

Project description:VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently described monogenic disease of adult men cause by somatic mutations in UBA1 in hematopoietic progenitor cells. It associates inflammatory-related symptoms, frequently involving the skin, and hematologic disorders. Myelodysplasia cutis, also recently described, is a cutaneous manifestation of myelodysplasia in which clonal myeloid cells infiltrate the skin. In both cases, skin lesions are due to the infiltration of clonal mutated myeloid cells and may clinically and histologically resemble sweet syndrome, a non-clonal neutrophilic skin disease. The aim of this study was to decipher the underlying mechanisms driving these three myeloid-related skin diseases using RNA-sequencing compared with healthy control skins and leukemia cutis, a neoplastic myeloid-related skin condition.

2025-04-01 | GSE245639 | GEO

Bone Marrow Mesenchymal Stromal Cells Support Translation in Refractory Acute Myeloid Leukemia

Project description:In acute myeloid leukemia (AML), malignant cells surviving chemotherapy rely on high mRNA translation and their microenvironmental metabolic support to drive relapse. However, the role of translational reprogramming in the niche is unclear. Here we found that relapsing AML cells increase translation in their bone marrow (BM) niches, where BM mesenchymal stromal cells (BMSCs) become a source of eIF4A-cap-dependent translation machinery that is transferred to AML cells via extracellular vesicles (EVs), to meet their translational demands. In two independent models of highly chemo-resistant AML driven by MLL-AF9 or FLT3-ITD;NPMc mutations, protein synthesis levels increase in refractory AML dependently on nestin+ BMSCs. Inhibiting cap-dependent translation in BMSCs abolishes their chemoprotective ability, while EVs from BMSCs carrying eIF4A boost AML cell translation and survival. Consequently, eIF4A inhibition synergizes with conventional chemotherapy. Together, these results suggest that AML cells rely on BMSCs to maintain an oncogenic translational program required for relapse

2024-12-27 | PXD058646 | Pride

Bone Marrow Mesenchymal Stromal Cells Support Translation in Refractory Acute Myeloid Leukemia

2025-01-07 | PXD058648 | Pride