Bone marrow RNA sequencing profiles from AML patients and healthy donors
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE317967 | GEO | 2026/03/01
REPOSITORIES: GEO
Similar Datasets
Project description:Acute myeloid leukemia (AML) with chromosomal rearrangements involving the H3K4 methyltransferase mixed-lineage leukemia (MLL) is an aggressive subtype with low overall survival. MLL rearrangements rapidly transform hematological stem and progenitor cell (HSPC) to leukemia stem cell (LSC). Bortezomib (Velcade) is used widely in hematological malignancies. However, it is still unknown whether bortezomib possesses anti-self-renewal and anti-leukemogenesis of LSC in AML with MLL rearrangements. Here, we found that bortezomib inhibited cell proliferation, induced apoptosis, and decreased colony formation in leukemic cell lines, primary AML blasts, and MLL-AF9-transformed murine leukemic blasts. Besides, bortezomib reduced the frequency and function of LSC, inhibited the progression, and prolonged
2022-08-10 | GSE157702 | GEO
Project description:MicroRNAs(miRNAs) are a class of small non-coding RNAs that have been shown to play a crucial role in normal hematopoiesis and leukemogenesis. In this study, we aimed to identify key miRNAs relevant to differentiation arrest in acute myeloid leukemia (AML). Next-generation small RNA sequencing (RNA-seq) was performed on paired bone marrow samples from 5 AML patients at initial diagnosis and first complete remission (CR). Differentially expressed miRNAs (DEMs) at initial diagnosis as compared to CR were analyzed for each case.
2023-12-27 | GSE244813 | 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 a clonal hematopoietic malignancy, characterized by expansion of immature leukemic blasts in the bone marrow. In AML, specific tyrosine kinases have been implicated in leukemogenesis, and are associated with poor treatment outcome. However, targeted therapy using kinase inhibitors (KIs) has had limited success, and may be improved by proper patient selection. We performed phosphotyrosine (pY) based, label-free phosphoproteomics to identify hyperphosphorylated, active kinases in two FLT3+ AML Pt samples.
2020-03-02 | PXD015639 | Pride
Project description:Unbalanced chromosomal abnormalities might play a major role in the leukemogenesis of AML-M5 Oligonucelotide array CGH were performed on 24 patients with AML-M5 To assess the possible existence of unbalanced chromosomal abnormalities and delineate the characterization of copy number alterations (CNAs) of acute myeloid leukemia-M5 (AML-M5)
2013-12-18 | E-GEOD-53429 | biostudies-arrayexpress
Project description:Genome-wide analysis of single nucleotide polymorphisms in 64 acute myeloid leukemias has revealed that 20% exhibited large regions of homozygosity that could not be accounted for by visible chromosomal abnormalities in the karyotype. Further analysis confirmed that these patterns were due to partial uniparental disomy (UPD). Remission bone marrow was available from five patients showing UPD in their leukemias, and in all cases the homozygosity was found to be restricted to the leukemic clone. Two examples of UPD11p were shown to be of different parental origin as indicated by the methylation pattern of the H19 gene. Furthermore, a previously identified homozygous mutation in the CEBPA gene coincided with a large-scale UPD on chromosome 19. These cryptic chromosomal abnormalities, which seem to be nonrandom, have the characteristics of somatic recombination events and may define an important new subclass of leukemia. Patient No. from Table 1 of Raghavan et al 2005 and Sample name; Patient No: 1 = Sample name: AML sample 35 diagnosis; Patient No: 1 = Sample name: AML sample 107 remission; Patient No: 2 = Sample name: AML sample 37 diagnosis; Patient No: 3 = Sample name: AML sample 10 diagnosis; Patient No: 3 = Sample name: AML sample 44 remission; Patient No: 4 = Sample name: AML sample 20 diagnosis; Patient No: 5 = Sample name: AML sample 65 diagnosis; Patient No: 6 = Sample name: AML sample 69 diagnosis; Patient No: 6 = Sample name: AML sample 94 remission; Patient No: 7 = Sample name: AML sample 40 diagnosis; Patient No: 7 = Sample name: AML sample 41 remission; Patient No: 8 = Sample name: AML sample 64 diagnosis; Patient No: 9 = Sample name: AML sample 7 diagnosis; Patient No: 10 = Sample name: AML sample 49 diagnosis; Patient No: 10 = Sample name: AML sample 106 remission; Patient No: 11 = Sample name: AML sample 76 diagnosis; Patient No: 12 = Sample name: AML sample 79 diagnosis Experiment Overall Design: DNA from 64 diagnostic AML samples were analysed using Affymetrix 10K SNP arrays. Large regions of homozygosity were identified and compared with remission bone marrow where available.
2008-06-15 | E-GEOD-7490 | biostudies-arrayexpress
Project description:Antibody-based therapy for cancer is now one of the most successful and important strategies for treating patients with hematological malignancies. However, the lack of efficient tumor-associated antigens restricts the targeting therapy of myeloid leukemia. Analysis of the gene expression proï¬les of primary bone marrow samples from human acute myeloid leukemia (AML) patients or healthy donors was to identify and expand novel targets for the treatment of myeloid leukemias. we found that epithelial cell adhesion molecule (EpCAM) is overexpressed in patients with AML. we analyzed the gene expression proï¬les of bone marrow mononuclear cells from 2 human acute myeloid leukemia (AML) patients and 2 healthy donors using an oligonucleotide microarray, to identify up-regulated genes in AML samples comparing with healthy tissues.
2016-05-14 | E-GEOD-79605 | biostudies-arrayexpress
Project description:Decitabine (DAC) is used clinically for myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). Our genome-wide CRISPR-dCas9 activation screen using MDS-derived AML cells shows that mitotic regulation plays a pivotal role in DAC resistance. DAC strongly induces abnormal mitosis (abscission failure or tripolar mitosis) in human myeloid tumors at clinical concentrations, especially in those with TP53 mutations and antecedent hematological disorders. This DAC-induced mitotic disruption and apoptosis are significantly attenuated in DNMT1-depleted cells. In contrast, the overexpression of Dnmt1, but not the catalytically inactive mutant, enhances DAC-induced mitotic defects in myeloid tumors. We also demonstrate that DAC-induced mitotic disruption is enhanced by pharmacological inhibition of the ATR-CLSPN-CHK1 pathway. These data challenge the current assumption that DAC inhibits leukemogenesis through DNMT1 inhibition and subsequent DNA hypomethylation, while highlighting the potent activity of DAC to perturb mitosis through aberrant DNMT1-DNA covalent bonds.
2023-08-14 | GSE240570 | GEO
Project description:Inflammation is a hallmark of cancer and is linked to patient prognosis in acute myeloid leukemia (AML). Our recent study revealed that hematopoietic stem and progenitor cells (HSPCs) exhibit an inflammatory active state and serve as a cellular source of inflammatory cytokine secretion in AML. Recent studies in infection and chronic inflammation related disease models have revealed that inflammation can reprogram HSPCs to fuel chronic inflammation related co-mobidities. Building on our report of AML-associated inflammation in HSPCs, here we ask whether AML-experienced normal HSPCs are reprogrammed in AML. To investigate this, we utilized a chimeric model of AML, carrying both doxycycline-inducible leukemic and healthy wildtype hematopoietic fractions, to generate an AML remission model. To test whether AML-experienced HSPCs harbor inflammatory memory, mice were challenged with heterogenous inflammatory activation. Our transcriptomic and epigenetic results show for the first time that phenotypically normal, AML-experienced HSPCs carry a durable inflammatory memory whereby primary exposure to AML secreted factors alters their response to secondary stimuli. Our finding suggests that AML-experienced HSPCs are innate immune reprogrammed in the AML niche.
2025-07-01 | GSE280873 | GEO
Project description:Inflammation is a hallmark of cancer and is linked to patient prognosis in acute myeloid leukemia (AML). Our recent study revealed that hematopoietic stem and progenitor cells (HSPCs) exhibit an inflammatory active state and serve as a cellular source of inflammatory cytokine secretion in AML. Recent studies in infection and chronic inflammation related disease models have revealed that inflammation can reprogram HSPCs to fuel chronic inflammation related co-mobidities. Building on our report of AML-associated inflammation in HSPCs, here we ask whether AML-experienced normal HSPCs are reprogrammed in AML. To investigate this, we utilized a chimeric model of AML, carrying both doxycycline-inducible leukemic and healthy wildtype hematopoietic fractions, to generate an AML remission model. To test whether AML-experienced HSPCs harbor inflammatory memory, mice were challenged with heterogenous inflammatory activation. Our transcriptomic and epigenetic results show for the first time that phenotypically normal, AML-experienced HSPCs carry a durable inflammatory memory whereby primary exposure to AML secreted factors alters their response to secondary stimuli. Our finding suggests that AML-experienced HSPCs are innate immune reprogrammed in the AML niche.
2025-07-01 | GSE280867 | GEO