Lymphoid subsets in the AML bone marrow microenvironment following chemotherapy induction
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE279904 | GEO | 2025/04/21
REPOSITORIES: GEO
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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 | GSE212615 | 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:Lymphoid subsets in the AML bone marrow microenvironment following chemotherapy induction
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Project description:1) Transcriptional profiles of highly purified (≥ 98%) PB CD8+ T-cells from newly diagnosed AML patients (pre-treatment) were compared to age-matched healthy controls and transcriptional profiles of PB AML CD8+ T-cells from patients who achieved complete remission (CR) versus non-responders (NR) longitudinally, at pre-treatment and upon recovery following induction chemotherapy (paired samples). 2) Transcriptional profiles of PB AML CD8+ T-cells from patients who achieved complete remission (CR) versus non-responders (NR) longitudinally, at pre-treatment (PRE) and upon recovery following induction chemotherapy (POST) (paired samples).
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Project description:Nucleophosmin mutated AML (NPM1mut-AML) patients have a high rate of complete remission (CR) to induction chemotherapy. However, the mechanisms responsible for such effects are unknown. Since miR-10 family members are expressed at high levels in NPM1mut-AML, we evaluated whether these microRNAs could predict chemotherapy response in AML. We found that high baseline miR-10 family expression in 54 untreated cytogenetically heterogeneous AML patients was associated with achieving CR. However, when we included NPM1 mutation status in the multivariable model, there was a significant interaction effect between miR-10a-5p expression and NPM1 mutation status. Similar results were observed when using a second cohort of 183 cytogenetically normal older (ageM-bM-^IM-%60 years) AML patients. Loss and gain of function experiments using miR-10a-5p in cell lines and primary blasts did not demonstrate any effect in apoptosis or cell proliferation at baseline or after chemotherapy. These data support a bystander role for the miR-10 family in NPM1mut-AML. Pretreatment miRNA expression was analyzed in 54 de novo adult AML patients obtained from the MD Anderson Cancer Center Leukemia Tissue Bank (LTB) using the Ohio State University (OSU) miRNA microarray (ver.3).
2014-05-01 | E-GEOD-55519 | biostudies-arrayexpress
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2025-04-04 | GSE288862 | GEO
Project description:The aim of our study was to evaluate the ability of miRNA expression patterns to predict chemotherapy response in a cohort of 39 patients with metastatic colorectal carcinoma To define miRNA signature, samples were obtained from tumor tissue samples of 39 patients . Patients were divided into responders or non-responders according to tresponse treatment with a chemotherapy regimen that included fluoropyrimidines and either oxaliplatin or irinotecan .Tumor response was evaluated by conventional methods according to the standard RECIST 1.0 criteria: a complete response (CR) was defined as the disappearance of all measurable and evaluable evidence of disease; a partial response (PR) was defined as a > 30% decrease in the sum of the longest diameters of target lesions; stable disease (SD) was considered if the tumor burden decreased less than 30% or increased less than 20%; and progressive disease (PD) was indicated by a >20% increase in the sum of the longest diameters of target lesions or the appearance of any new lesion. Patients were classified according to best response to chemotherapy in two groups: those that achieved an objective response (Responders [R]: CR + PR) and those that did not (Non-responders [NR]: SD + PD). Mature human miRNA expression was detected and quantified using the TaqMan® Low Density Arrays (TLDA). The Human MicroRNA Card Set v2.0 array is a two card set containing a total of 384 TaqMan® MicroRNA Assays per card to enable accurate quantification of 667 human microRNAs, all catalogued in the miRBase database. Expression of target miRNAs was normalized in relation to the expression of MammU6. Cycle threshold (Ct) values were calculated using the SDS software v.2.3 using automatic baseline settings and a threshold of 0.2. Relative quantification of miRNA expression was calculated by the 2−ΔCt method (Applied Biosystems user bulletin no. 2 (P/N 4303859)).
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Project description:Extracellular vesicle (EV) trafficking provides for a constitutive mode of cell-cell communication within tissues and between organ systems. Different EV subtypes have been identified that transfer regulatory molecules between cells, influencing gene expression, and altering cellular phenotypes. Evidence from a range of studies suggests that EV trafficking enhances cell survival and resistance to chemotherapy in solid tumors. In acute myeloid leukemia (AML), EVs contribute to the dynamic crosstalk between AML cells, hematopoietic elements and stromal cells and promote adaptation of compartmental bone marrow (BM) function through transport of protein, RNA, and DNA. Careful analysis of leukemia cell EV content and phenotypic outcomes provide evidence that vesicles are implicated in transferring several known key mediators of chemoresistance, including miR-155, IL-8, and BMP-2. Here, we review the current understanding of how EVs exert their influence in the AML niche, and identify research opportunities to improve outcomes for relapsed or refractory AML patients.
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