Exome sequencing from multiple samples of AML patients - samples
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ABSTRACT:
PROVIDER: EGAD00001002728 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:<p>Acute Myeloid Leukemia (AML) commonly relapses after initial chemotherapy response. We assessed metabolic adaptations in chemoresistant cells in vivo before overt relapse, identifying altered branched-chain amino acid (BCAA) levels in patient-derived xenografts (PDX) and immunophenotypically identified leukemia stem cells from AML patients. Notably, this was associated with increased BCAA transporter expression with low BCAA catabolism. Restricting of BCAAs further reduced chemoresistant AML cells but relapse still occurred. Among the persisting cells we found an unexpected increase in protein production. This was accompanied by elevated translation of 2-oxoglutarate-and-iron-dependent oxygenase 1 (OGFOD1), a known ribosomal dioxygenase that adjusts the fidelity of tRNA anticodon pairing with coding mRNA1–3 and upregulates protein synthesis in AML driving disease aggressiveness. Inhibiting OGFOD1 impaired translation processing, decreased protein synthesis and improved animal survival even with chemoresistant AML through regulation of protein synthesis. Leukemic cells can therefore persist despite the stress of chemotherapy and nutrient deprivation through adaptive control of translation while sparing normal hematopoiesis. Targeting OGFOD1 may offer a distinctive, translation modifying means of reducing the chemopersisting cells that drive relapse.</p>
2025-07-19 | MTBLS10255 | MetaboLights
Project description:CITE-seq was used to interrogate transcriptomic and surface immunophenotype heterogeneity at diagnosis and relapse. This experiment reveals cell state evolution of AML blasts at two timepoints and provides new therapeutic avenues for targeting surface antigens in AML.
2026-01-12 | E-MTAB-16321 | biostudies-arrayexpress
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
Project description:In this unique study, based on paired samples obtained at AML diagnosis and at relapse, we assessed 380 multidrug-resistance-related genes, using TaqMan-based qRT-PCR, as indicated by reports published over the past three decades. 11 paired AML samples taken at diagnosis and at relapse after treatment. Each patients act as its own control.
2013-05-31 | E-GEOD-33787 | biostudies-arrayexpress
Project description:Acute Myeloid Leukemia (AML) commonly relapses after initial chemotherapy response. We assessed metabolic adaptations in a minimal-residual disease setting of chemoresistant cells in vivo before overt relapse, identifying elevated branched-chain amino acid (BCAA) levels in patient-derived xenografts (PDX) and immunophenotypically identified leukemia stem cells from AML patients. Notably, this was associated with increased BCAA transporter expression without indications for higher BCAA catabolism. Restricting of BCAAs further reduced chemoresistant AML cells but relapse still occurred. Among the persisting cells we found an unexpected Acute Myeloid Leukemia (AML) commonly relapses after initial chemotherapy response. We assessed metabolic adaptations in chemoresistant cells in vivo before overt relapse, identifying altered branched-chain amino acid (BCAA) levels in patient-derived xenografts (PDX) and immunophenotypically identified leukemia stem cells from AML patients. Notably, this was associated with increased BCAA transporter expression with low BCAA catabolism. Restricting of BCAAs further reduced chemoresistant AML cells but relapse still occurred. Among the persisting cells we found an unexpected increase in protein production. This was accompanied by elevated translation of 2-oxoglutarate-and-iron-dependent oxygenase 1 (OGFOD1), a known ribosomal dioxygenase that adjusts the fidelity of tRNA anticodon pairing with coding mRNA1–3 and upregulates protein synthesis in AML driving disease aggressiveness. Inhibiting OGFOD1 impaired translation processing, decreased protein synthesis and improved animal survival even with chemoresistant AML through regulation of protein synthesis. Leukemic cells can therefore persist despite the stress of chemotherapy and nutrient deprivation through adaptive control of translation while sparing normal hematopoiesis. Targeting OGFOD1 may offer a distinctive, translation modifying means of reducing the chemopersisting cells that drive relapse.
2025-11-18 | GSE292851 | GEO
Project description:Expression of proteins regulating apoptosis (BCL-2, MCL-1, BCL-X and BAX) in acute myeloid leukemia (AML) blasts at diagnosis have been shown to be associated with disease-free survival. We previously found that the initially high apoptosis-resistance of AML cells decreased after therapy, while regaining high levels at relapse. This suggested a dynamic regulation of apoptosis. We hypothesized that expression of apoptosis-related proteins in AML blasts, and possibly also in bystander cells in the bone marrow, is regulated by extracellular factors present in the AML microenvironment. Tumor cell communication with its microenvironment is emerging as an important determinant playing multiple roles in cancer. Both soluble factors and extracellular vesicles (EVs), most notably exosomes, have been shown to influence cellular processes of malignant and normal cells in the tumor microenvironment. We performed a proteomics analysis of the whole secretome as well as of EVs secreted by AML blasts to pinpoint released protein factors that might mediate apoptosis-resistance.
2016-10-21 | MSV000080268 | MassIVE
Project description:Pediatric acute myeloid leukemia (AML) bone marrow (BM) samples from diagnosis (Dx), end of induction (EOI), and relapse timepoints were analyzed by single-cell RNA sequencing (scRNA-seq). Analysis of matched Dx, EOI scRNA-seq datasets and TARGET AML RNA-seq datasets revealed a novel AML blasts-associated 7-gene signature (CLEC11A, PRAME, AZU1, NREP, ARMH1, C1QBP, TRH) that was validated in two independent datasets. Distinct clusters of relapse- and continuous complete remission (CCR)-associated AML-blasts were observed at Dx, with differential expression of genes associated with survival. At Dx, relapse-associated samples had more exhausted T cells while CCR-associated samples had more inflammatory M1 macrophages. Post-therapy EOI residual blasts overexpressed fatty acid oxidation, tumor growth, and stemness genes. Also, a post-therapy T-cells cluster present in relapse-associated samples exhibited downregulation of MHC Class I and T-cell regulatory genes. Altogether, this study deeply characterizes pediatric AML relapse- and CCR-associated samples to provide novel insights into BM microenvironment landscape.
2023-09-05 | GSE235923 | GEO
Project description:Acute myeloid leukemia (AML) is a hematological cancer that affects mainly the elderly. Although complete remission (CR) is achieved for the majority of the patients after induction and consolidation therapies, nearly two-thirds relapse within a short interval. Therefore, understanding of the biological factors that determine relapse has become a major interest in clinical AML. In order to identify the proteins and their phosphorylated modifications involved in AML relapse, we performed a global proteome and phosphoproteome study by liquid chromatography tandem mass spectrometry (LC-MS/MS) with primary cells from 41 AML patients at time of diagnosis that were defined as RELAPSE or REL_FREE according to their relapse status after a 5-year clinical follow-up post diagnosis. Our findings showed that the diagnostic sample of patients relapsing had increased levels of RNA processing and decreased expression of V-ATPases proteins along with CDKs and CSK2 activities. LC-MS/MS-based results were further validated with cell proliferation assays using V-ATPase inhibitor bafilomycin A1, CSK2 inhibitor CX-4945, CDK4/6 inhibitor abemaciclib and CDK2/7/9 inhibitor SNS-032. Our study presents molecules that could predict AML relapse and direct new therapeutic strategies that might circumvent more aggressive AML episodes.
2020-04-14 | PXD014997 | Pride
Project description:Acute myeloid leukemia (AML) is an aggressive cancer which causes the rapid proliferation of immature myeloid-lineage blood cells (myeloblasts) in the bone marrow. These leukemic cells receive trophic signals from the bone marrow micro-environment (BMM) in which they reside, that are essential to the initiation and maintenance of the disease. Because this is a complex and heterogeneous tissue, many aspects of this environment remain poorly characterised due to experimental hurdles. Here we performed single-cell RNA-sequencing of bone marrow aspirates from 10 AML patients across multiple key timepoints in disease progression (diagnosis, post-treatment, relapse).
2023-06-13 | GSE227903 | GEO
Project description:Acute myeloid leukemia (AML) is characterized by serious aggressivity of high relapse risk and various molecular aberrations. Rearrangements involving NUP98 with multiple fusing partner genes in myeloid malignancies indicate dismal survival outcomes. Mechanisms contributing to subsequent aggressive progression and severe relapse risk of NUP98-rearranged AML remain undefined. Here we identified a novel oncogenic fusion RUNX1/ZNF423 in a relapse and refractory AML patient with NUP98/NSD1. And mice xenografted from the patient bearing both RUNX1/ZNF423 and NUP98/NSD1 display more severe engraftment levels than NUP98/NSD1 only. Mechanically, RUNX1/ZNF423 accompanied with NUP98/NSD1 recapitulated transcriptional signatures in hematopoietic differentiation blockage and altered amino acid metabolism pathway. Moreover, single-cell sequencing confirmed the coexistence of RUNX1/ZNF423 with NUP98/NSD1 in the same leukemic blast. Meanwhile, we also found that the coexistence of gene fusions in NUP98-rearranged AML was a significant phenomenon, which probably contributes to their worse clinical outcome. Finally, tailored intervention treatment based on ex vivo drug sensitivity testing is provided to this relapse and refractory AML patient and achieved favorable clinical response. Taken together, we not only identified a novel gene fusion RUNX1/ZNF423 with transforming potential detected in a NUP98-rearranged AML, but also achieved a deeper understanding into mechanisms contributing to disease relapse in AML.
2024-12-01 | GSE222098 | GEO