Blast cells surviving acute myeloid leukemia induction therapy are in cycle with a signature of FOXM1 activity
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE162542 | GEO | 2021/10/04
REPOSITORIES: GEO
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Project description:Acute myeloid leukemia (AML) represent a series of hemopathies characterized by the clonal expansion in bone marrow and blood of immature myeloid cells blocked in differentiation, called blasts. Despite significant supportive care progresses, few medical discoveries radically changed LAM prognosis (5 year survival rate of 30%). An aggressive conventional chemotherapy is used to kill AML cells. However, many patients relapse mainly due to the persistence of rare AML cells able to re-initiate the disease. Quiescence and protection against environmental stresses (chemoresistance) are major characteristics of these cells. Drug efflux leading to chemoresistance is observed by Side Population (SP) detection through ABC transporter activation. So, AML blasts presenting SP functionality could represent a chemoresistant population. This SP phenotype is essentially acquired by circulating AML blasts after contact with medullar mesenchymal stromal cells (MSC). A transcriptome analysis of AML blasts sorted according to their SP functionality or not (Non SP cells or Main Population, ie MP) after co-culture on MSCs was realized.
2020-01-18 | GSE114633 | GEO
Project description:Acute myeloid leukemia (AML) is a heterogeneous group of malignancies which may be sensitive to the natural killer (NK) cell anti-tumor response. However, NK cells are frequently defective in AML. Here, we found in an exploratory cohort (n = 46) that NK-cell status at diagnosis of AML separated patients in two groups with a different clinical outcome. Patients with a deficient NK-cell profile, including reduced expression of some activating NK receptors (e.g. DNAM-1, NKp46 and NKG2D) and decreased IFN-g production, had a significantly higher risk of relapse (P = 0.03) independently of cytogenetic classification in multivariate analysis. Patients with defective NK cells showed a profound gene expression decrease in AML blasts for cytokine and chemokine signaling (e.g. IL15, IFNGR1, IFNGR2, CXCR4), antigen processing (e.g. HLA-DRA, HLA-DRB1, CD74) and adhesion molecule pathways (e.g. PVR, ICAM1). A set of 388 leukemic classifier genes defined in the exploratory cohort was independently validated in a multicentric cohort of 194 AML patients. In total, these data evidenced the interplay between NK-cells and AML blasts at diagnosis allowing an immune-based stratification of AML patients independently of clinical classifications. 5 normal AML cells were compared with 8 NK deficient AML cells.
2015-07-24 | E-GEOD-50928 | biostudies-arrayexpress
Project description:Acute myeloid leukemia (AML) is a heterogeneous group of malignancies which may be sensitive to the natural killer (NK) cell anti-tumor response. However, NK cells are frequently defective in AML. Here, we found in an exploratory cohort (n = 46) that NK-cell status at diagnosis of AML separated patients in two groups with a different clinical outcome. Patients with a deficient NK-cell profile, including reduced expression of some activating NK receptors (e.g. DNAM-1, NKp46 and NKG2D) and decreased IFN-g production, had a significantly higher risk of relapse (P = 0.03) independently of cytogenetic classification in multivariate analysis. Patients with defective NK cells showed a profound gene expression decrease in AML blasts for cytokine and chemokine signaling (e.g. IL15, IFNGR1, IFNGR2, CXCR4), antigen processing (e.g. HLA-DRA, HLA-DRB1, CD74) and adhesion molecule pathways (e.g. PVR, ICAM1). A set of 388 leukemic classifier genes defined in the exploratory cohort was independently validated in a multicentric cohort of 194 AML patients. In total, these data evidenced the interplay between NK-cells and AML blasts at diagnosis allowing an immune-based stratification of AML patients independently of clinical classifications. Gene expression analysis were performed on CD56bright and CD56dim NK cells sorted from patients with impaired or normal CD56bright NK cells (n=2 for each patients? group) and from 3 HC
2015-07-24 | E-GEOD-34885 | biostudies-arrayexpress
Project description:Acute myeloid leukemia (AML) is a heterogeneous group of malignancies which may be sensitive to the natural killer (NK) cell anti-tumor response. However, NK cells are frequently defective in AML. Here, we found in an exploratory cohort (n = 46) that NK-cell status at diagnosis of AML separated patients in two groups with a different clinical outcome. Patients with a deficient NK-cell profile, including reduced expression of some activating NK receptors (e.g. DNAM-1, NKp46 and NKG2D) and decreased IFN-g production, had a significantly higher risk of relapse (P = 0.03) independently of cytogenetic classification in multivariate analysis. Patients with defective NK cells showed a profound gene expression decrease in AML blasts for cytokine and chemokine signaling (e.g. IL15, IFNGR1, IFNGR2, CXCR4), antigen processing (e.g. HLA-DRA, HLA-DRB1, CD74) and adhesion molecule pathways (e.g. PVR, ICAM1). A set of 388 leukemic classifier genes defined in the exploratory cohort was independently validated in a multicentric cohort of 194 AML patients. In total, these data evidenced the interplay between NK-cells and AML blasts at diagnosis allowing an immune-based stratification of AML patients independently of clinical classifications.
2015-07-24 | GSE34885 | GEO
Project description:Acute myeloid leukemia (AML) is a heterogeneous group of malignancies which may be sensitive to the natural killer (NK) cell anti-tumor response. However, NK cells are frequently defective in AML. Here, we found in an exploratory cohort (n = 46) that NK-cell status at diagnosis of AML separated patients in two groups with a different clinical outcome. Patients with a deficient NK-cell profile, including reduced expression of some activating NK receptors (e.g. DNAM-1, NKp46 and NKG2D) and decreased IFN-g production, had a significantly higher risk of relapse (P = 0.03) independently of cytogenetic classification in multivariate analysis. Patients with defective NK cells showed a profound gene expression decrease in AML blasts for cytokine and chemokine signaling (e.g. IL15, IFNGR1, IFNGR2, CXCR4), antigen processing (e.g. HLA-DRA, HLA-DRB1, CD74) and adhesion molecule pathways (e.g. PVR, ICAM1). A set of 388 leukemic classifier genes defined in the exploratory cohort was independently validated in a multicentric cohort of 194 AML patients. In total, these data evidenced the interplay between NK-cells and AML blasts at diagnosis allowing an immune-based stratification of AML patients independently of clinical classifications.
2015-07-24 | GSE50928 | 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. Herein, we further explored this aspect of apoptosis in AML. Firstly, the intra-individual ex vivo apoptosis-related profiles of normal lymphocytes and AML blasts showed a strong correlation, with expression values far beyond control lymphocytes. Secondly, we demonstrated that apoptosis-resistant primary AML blasts, as opposed to apoptosis-sensitive cells, were able to up-regulate BCL-2 expression in sensitive AML blasts in contact cultures (p=0.0067 and p=1.0 respectively). Using proteomics we further set out to identify novel proteins possibly engaged in apoptosis regulation. Proteomics analysis revealed that major functional protein clusters upregulated in secretomes of apoptosis-resistant AML, were presumably engaged in global gene regulation including mRNA splicing, protein translation and chromatin remodeling.
2016-02-03 | PXD001476 | Pride
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: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. This data is from the lysate fraction of the secretomes described in PXD001476.
2016-02-03 | PXD003471 | Pride
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.
2016-02-03 | PXD001487 | Pride
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