Transcriptomics of AML core bone marrow biopsies reveals distinct therapy response-specific osteo-mesenchymal profiles [microarray]
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ABSTRACT:
PROVIDER: PRJNA878839 | ENA |
REPOSITORIES: ENA
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Project description:While the bone marrow (BM) microenvironment is significantly remodeled in acute myeloid leukemia (AML), our understanding of chemotherapy-induced changes within the BM stroma and their involvement in disease recurrence remains limited. Molecular insight into AML-specific alterations in the microenvironment has been historically limited by the analysis of liquid marrow aspirates rather than core biopsies that contain solid-phase BM stroma with non-hematopoietic cells supporting hematopoiesis. We assessed the effect of standard anthracycline- and cytarabine-based induction chemotherapy on both hematopoietic and non-hematopoietic cells directly in core BM biopsies using RNA-seq and histological analysis to determine the transcriptomic profile and factors associated with the response to treatment. We compared matched human core BM biopsies at diagnosis and 2 weeks after standard cytarabine/anthracycline induction therapy in responders (<5% blasts present post-treatment ) and non-responders (>5% blasts present post-treatment). Our data indicated enrichment in vimentin (VIM), platelet-derived growth factor receptor beta (PDGFRB) and Snail family transcriptional repressor 2(SNAI2) transcripts in responders, consistent with the reactivation of the mesenchymal population in the BM stroma. Enrichment of osteoblast maturation-related transcripts of biglycan (BGN), osteopontin (SPP1), and osteonectin (SPARC) was observed in core BM biopsies from non-responders to induction chemotherapy. To the best of our knowledge, this is the first report demonstrating distinct osteogenic and mesenchymal transcriptome profiles specific to AML BM response to induction chemotherapy assessed directly in core BM biopsies. Detailing treatment response-specific alterations in the BM stroma may inform optimized therapeutic strategies for AML.
2023-01-30 | GSE213056 | GEO
Project description:While the bone marrow (BM) microenvironment is significantly remodeled in acute myeloid leukemia (AML), our understanding of chemotherapy-induced changes within the BM stroma and their involvement in disease recurrence remains limited. Molecular insight into AML-specific alterations in the microenvironment has been historically limited by the analysis of liquid marrow aspirates rather than core biopsies that contain solid-phase BM stroma with non-hematopoietic cells supporting hematopoiesis. We assessed the effect of standard anthracycline- and cytarabine-based induction chemotherapy on both hematopoietic and non-hematopoietic cells directly in core BM biopsies using RNA-seq and histological analysis to determine the transcriptomic profile and factors associated with the response to treatment. We compared matched human core BM biopsies at diagnosis and 2 weeks after standard cytarabine/anthracycline induction therapy in responders (<5% blasts present post-treatment ) and non-responders (>5% blasts present post-treatment). Our data indicated enrichment in vimentin (VIM), platelet-derived growth factor receptor beta (PDGFRB) and Snail family transcriptional repressor 2(SNAI2) transcripts in responders, consistent with the reactivation of the mesenchymal population in the BM stroma. Enrichment of osteoblast maturation-related transcripts of biglycan (BGN), osteopontin (SPP1), and osteonectin (SPARC) was observed in core BM biopsies from non-responders to induction chemotherapy. To the best of our knowledge, this is the first report demonstrating distinct osteogenic and mesenchymal transcriptome profiles specific to AML BM response to induction chemotherapy assessed directly in core BM biopsies. Detailing treatment response-specific alterations in the BM stroma may inform optimized therapeutic strategies for AML.
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Project description:Transcriptomics of AML core bone marrow biopsies reveals distinct therapy response-specific osteo-mesenchymal profiles
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Project description:Transcriptomics of AML core bone marrow biopsies reveals distinct therapy response-specific osteo-mesenchymal profiles by RNA-seq and microarray analysis
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Project description:Glioblastoma, IDH wild type (GBM) is a primary brain cancer with a poor prognosis and few effective therapies. The ability to investigate the tumor and its microenvironment during treatment would greatly enhance understanding of disease response, progression and impact of therapeutics. Stereotactic needle core biopsies are routine surgical procedures performed primarily for tumor diagnosis. Use of these biopsies for investigations into tumor and microenvironmental responses to treatment is rarely performed but holds great potential to support therapeutic monitoring and understanding of tumor evolution. However, it is unclear whether needle core biopsies are sufficient for multi-omics analysis and tumor models. Here we test the depth of data generation possible from stereotactic needle core biopsy tissue in two separate patients. In the first patient with recurrent GBM we performed highly resolved multi-omics analyses including single cell RNA sequencing, spatial-transcriptomics, metabolomics, proteomics, phosphoproteomics, T-cell clonotype analysis, and MHC Class I immunopeptidomics from biopsy tissue obtained from a single procedure. In a second patient we analyzed multi-regional core biopsies to decipher spatial and genomic variance and quantify intra and inter-sample heterogeneity. We also investigated the utility of stereotactic biopsies as a method for generating patient derived xenograft (PDX) models in a separate patient cohort. Dataset integration across modalities highlighted spatially mapped immune cell associated metabolic pathways, revealed poor correlation between RNA expression and the tumor MHC Class I immunopeptidome, and validated inferred cell-cell ligand receptor interactions. In conclusion, stereotactic needle biopsy cores are of sufficient quality to generate multi-omics data and PDX models, provide data rich insight into a patient’s disease process and tumor immune microenvironment and can be of value in evaluating treatment responses.
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