Bone marrow microenvironment mediated drug resistance in Acute promyelocytic leukemia
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PROVIDER: PRJNA514741 | ENA |
REPOSITORIES: ENA
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Project description:About 5-10% newly diagnosed and about 20-30% of relapsed acute promyelocytic leukemia (APL) patients will have disease recurrence after receiving currently accepted standards of care. While there are reports of micro-environment mediated drug resistance (EM-DR) in AML, there is no data on the effect of malignant promyelocyte and stromal interaction on Arsenic trioxide (ATO) induced apoptosis. There are limited study available on the effect of leukemic cell interaction on stromal cells. We undertook a preliminary study to evaluate the changes induced by leukemic cells on stromal cells. In a gene expression profiling comparing HS-5 cells in co-culture with NB4 cells alone, 8456 genes were differentially regulated. On a preliminary analysis, we observed an up-regulation of various pathways such as adhesion, Cytokines, Wnt signalling in the stromal cells.
2020-01-10 | GSE124987 | GEO
Project description:About 5-10% newly diagnosed and about 20-30% of relapsed acute promyelocytic leukemia (APL) patients will have disease recurrence after receiving currently accepted standards of care. While there are reports of micro-environment mediated drug resistance (EM-DR) in AML, there is no data on the effect of malignant promyelocyte and stromal interaction on Arsenic trioxide (ATO) induced apoptosis. We undertook a preliminary study to evaluate the role of EM-DR to ATO in APL. In direct co-culture (contact dependent system) of malignant promyelocyte with stromal cells, the stromal cells gave a significant protective effect against ATO at different concentrations used (1 to 8 μmol; NB4 (APL cell line) In a gene expression profiling comparing NB4 cells in co-culture with NB4 cells alone, 1846 genes were differentially regulated. On a preliminary analysis, we observed an up-regulation of various pathways such as adhesion (ITGB1, ITGB2, ITGB7, etc.), Cytokines (IL-6, IL-8, IL-18, CCL2, CCL10, etc.) Wnt signalling (Wnt5a, Wnt11, NFATC4, etc,) NF-kB pathway (ICAM1, BIRC2, BIRC3, XIAP1, etc.) in the leukemic cells. The NF-kB pathway has been validated using real time PCR which correlated with the genes being differentially regulated in NB4 cells co-cultured in stroma. Agilent one-color experiment,Organism: Homo sapiens ,Custom Agilent 8x60k Human Whole Genome Microarray Gene expression (AMADID: 039494) , Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442)
2016-09-01 | E-GEOD-73157 | biostudies-arrayexpress
Project description:About 5-10% newly diagnosed and about 20-30% of relapsed acute promyelocytic leukemia (APL) patients will have disease recurrence after receiving currently accepted standards of care. While there are reports of micro-environment mediated drug resistance (EM-DR) in AML, there is no data on the effect of malignant promyelocyte and stromal interaction on Arsenic trioxide (ATO) induced apoptosis. We undertook a preliminary study to evaluate the role of EM-DR to ATO in APL. In direct co-culture (contact dependent system) of malignant promyelocyte with stromal cells, the stromal cells gave a significant protective effect against ATO at different concentrations used (1 to 8 μmol; NB4 (APL cell line) In a gene expression profiling comparing NB4 cells in co-culture with NB4 cells alone, 1846 genes were differentially regulated. On a preliminary analysis, we observed an up-regulation of various pathways such as adhesion (ITGB1, ITGB2, ITGB7, etc.), Cytokines (IL-6, IL-8, IL-18, CCL2, CCL10, etc.) Wnt signalling (Wnt5a, Wnt11, NFATC4, etc,) NF-kB pathway (ICAM1, BIRC2, BIRC3, XIAP1, etc.) in the leukemic cells. The NF-kB pathway has been validated using real time PCR which correlated with the genes being differentially regulated in NB4 cells co-cultured in stroma.
2016-09-01 | GSE73157 | GEO
Project description:Investigation of bone marrow microenvironment-induced drug resistance in acute lymphoblastic leukemia (ALL)
| PRJNA822779 | ENA
Project description:Chronic myeloid leukemia (CML) cells circulate between blood and bone marrow niche, representing different microenvironments. We studied the role of the two RNA binding proteins, T-cell-restricted intracellular antigen (TIAR) and the fragile X mental retardation protein (FMRP) in the regulation of protein translation in CML cells residing in settings mimicking peripheral blood microenvironment (PBM) and bone marrow microenvironment (BMM). We studied how conditions shaped the translation process through TIAR and FMRP activity, considering its relevance in therapy resistance. The QuaNCAT mass-spectrometric approach revealed that TIAR and FMRP have a discrete modulatory effect on protein synthesis and thus affect distinct aspects of leukemic cells functioning in the hypoxic niche. We demonstrate that TIAR substantially supports the resistance of CML cells to translation inhibition by homoharringtonine in the BMM. Overall, our results show that targeting post-transcriptional control should be considered when designing anti-leukemia therapeutic solutions.
2023-05-10 | PXD032332 | Pride
Project description:The bone marrow microenvironment of leukemia plays a key role in leukemia progression, but its molecular complexity in pre-B acute lymphoblastic leukemia (B-ALL), the most common cancer in children, remains poorly understood. Here we use single-cell RNA sequencing to characterise the bone marrow microenvironment during B-ALL progression.
2020-07-27 | GSE148115 | GEO
Project description:Glucocorticoids (GCs) and topoisomerase II inhibitors are used in the treatment of acute lymphoblastic leukaemia (ALL) due to their ability to induce cell death in lymphoid cells. GC-induced apoptosis is mediated by the glucocorticoid receptor (GR), whereas topoisomerase II inhibitors cause DNA damage and activate sensors of DNA damage including the tumour suppressor p53. In order to shed light on the role of the microenvironment in cell death and identify determinants of drug sensitivity we performed transcriptomic analysis in ALL cells treated with the synthetic glucocorticoid dexamethasone, and the topoisomerase II inhibitor etoposide combined with bone marrow-derived conditioned media (CM).
2017-08-30 | E-MTAB-4761 | biostudies-arrayexpress
Project description:Bulk RNA-seq of B-ALL cells cocultured with bone marrow-mesenchymal stem cells (BM-MSC) identified that B-ALL acquire epithelial-mesenchymal transition (EMT) properties by interacting with primary bone marrow-mesenchymal stem cells (BM-MSC) and scRNA-seq dissected the hybrid cluster of adherent B-ALL (Adh B-ALL) harboring B-ALL and BM-MSC features induced by EMT program
2022-05-31 | GSE200039 | GEO
Project description:The myeloma bone marrow microenvironment drives proliferation of malignant plasma cells and promotes resistance to therapy. Interleukin-6 (IL-6) and downstream JAK/STAT signaling are thought to be central components of these microenvironment-induced phenotypes. In a prior drug repurposing screen, we identified tofacitinib, a pan-JAK inhibitor FDA-approved for rheumatoid arthritis, as an agent that may reverse the tumor-stimulating effects of bone marrow mesenchymal stromal cells.Here, we validated both in vitro, in stromal-responsive human myeloma cell lines, and in vivo, in orthotopic disseminated murine xenograft models of myeloma, that tofacitinib showed both single-agent and combination therapeutic efficacy in myeloma models. Surprisingly, we found that ruxolitinib, an FDA-approved agent targeting JAK1 and JAK2, did not lead to the same anti-myeloma effects. Combination with a novel irreversible JAK3-selective inhibitor also did not rescue ruxolitinib effects. RNA-seq and unbiased phosphoproteomics revealed that marrow stromal cells drive a JAK/STAT-mediated proliferative program in myeloma plasma cells, and tofacitinib reversed the large majority of these pro-growth signals. Taken together, our results suggest that tofacitinib specifically reverses the growth-promoting effects of the tumor microenvironment through blocking an IL-6-mediated signaling axis. As tofacitinib is already FDA-approved, these results can be rapidly translated into potential clinical benefits for myeloma patients.
2018-10-24 | PXD006581 | Pride
Project description:To identify the genes that are differntially expressed in the bone marrow microenvironment of mice with leukemia we isolated total RNA from primary stromal cells sorted from mice with chronic or acute myeloid leukemia.
2022-06-15 | GSE205872 | GEO