Project description:The aim of the study was to get insights into transcriptional alterations in bone marrow mesenchymal stromal cells derived from acute myeloid leukemia patients We compared the global gene expression profile from AML BM-MSC (n=19) to healthy donor (HD) controls (HD BM-MSC n=4)
Project description:Human bone marrow mesenchymal stromal cells (BM-MSC) could be committed toward a functional lymphoid-like stroma by a combination of TNFalpha (TNF) and Lymphotoxin alpha1/beta2 (LT) (Amé-Thomas et al Blood 2007). Bone marrow and lymph node stromal cells support FL malignant cell recruitment and growth in particular after comittment to a lymphoid-like differentiation in vitro. In addition, more than 70% of FL patients exhibit a bone marrow involvment at diagnosis. We delineate using Affymetrix U133+2.0 microarrays the gene expression profile of BM-MSC obtained from FL patients (FL-MSC) and age-matched healthy donors (HD-MSC) in order to identify a specific FL-MSC signature. In addition, we used Affymetrix microarrays to define the gene expression signature of lymphoid-like stromal cells obtained from HD-MSC by treatment with TNF/LT in vitro. This TNF/LT signature was then used to interpret the gene expression profile of FL-MSC.
Project description:The aim of the study was to get insights into transcriptional alterations in bone marrow mesenchymal stromal cells derived from acute myeloid leukemia patients We compared the global gene expression profile from AML BM-MSC (n=19) to healthy donor (HD) controls (HD BM-MSC n=4) AML BM-MSC and HD BM-MSC were isolated from bone marrow aspirates (see below) and hybridized on an Affymetrix HG-U133 Plus 2.0 GeneChip
Project description:Human bone marrow mesenchymal stromal cells (BM-MSC) could be committed toward a functional lymphoid-like stroma by a combination of TNFalpha (TNF) and Lymphotoxin alpha1/beta2 (LT) (Amé-Thomas et al Blood 2007). Bone marrow and lymph node stromal cells support FL malignant cell recruitment and growth in particular after comittment to a lymphoid-like differentiation in vitro. In addition, more than 70% of FL patients exhibit a bone marrow involvment at diagnosis. We delineate using Affymetrix U133+2.0 microarrays the gene expression profile of BM-MSC obtained from FL patients (FL-MSC) and age-matched healthy donors (HD-MSC) in order to identify a specific FL-MSC signature. In addition, we used Affymetrix microarrays to define the gene expression signature of lymphoid-like stromal cells obtained from HD-MSC by treatment with TNF/LT in vitro. This TNF/LT signature was then used to interpret the gene expression profile of FL-MSC. GEP was performed on 10 BM-MSC from FL patients and 6 from healthy donors, treated or not with TNF(10 ng/mL)/LT(100ng/mL)
Project description:Bone marrow (BM) involvement is a common feature of lymphomas deriving from germinal-center B cells and is associated with a bad prognosis. In particular, follicular lymphoma (FL) infiltrates the BM in 70% of cases, in association with a remodeling of surrounding tumor microenvironment. Analysis of in vitro-expanded FL mesenchymal stromal cells (MSCs) revealed an extensive alteration of BM stromal cell phenotypic, transcriptomic, and functional profiles. However, the mechanisms supporting the direct interplay between lymphoma B cells and their permissive stromal niche in situ have not been yet identified. In the current work, we identified in the BM milieu of FL patients a deregulation of soluble and extracellular matrix (ECM) components reflecting inflammation and ectopic differentiation into lymphoid-like stromal cells. We reproduced the same alterations in a murine model of lymphoma B-cell xenograft where a scRNAseq approach identified LepRpos MSCs as specifically and progressively reprogramed by tumor B-cell invasion. Analysis of FL BM collected before and after treatment confirmed that BM niche was partly dependent on the continuous contact with tumor B cells. Altogether, this work shed new lights on the kinetic and mechanisms of BM stromal niche reshaping in B-cell lymphoma.
Project description:Bone marrow (BM) involvement is a common feature of lymphomas deriving from germinal-center B cells and is associated with a bad prognosis. In particular, follicular lymphoma (FL) infiltrates the BM in 70% of cases, in association with a remodeling of surrounding tumor microenvironment. Analysis of in vitro-expanded FL mesenchymal stromal cells (MSCs) revealed an extensive alteration of BM stromal cell phenotypic, transcriptomic, and functional profiles. However, the mechanisms supporting the direct interplay between lymphoma B cells and their permissive stromal niche in situ have not been yet identified. In the current work, we identified in the BM milieu of FL patients a deregulation of soluble and extracellular matrix (ECM) components reflecting inflammation and ectopic differentiation into lymphoid-like stromal cells. We reproduced the same alterations in a murine model of lymphoma B-cell xenograft where a scRNAseq approach identified LepRpos MSCs as specifically and progressively reprogramed by tumor B-cell invasion. Analysis of FL BM collected before and after treatment confirmed that BM niche was partly dependent on the continuous contact with tumor B cells. Altogether, this work shed new lights on the kinetic and mechanisms of BM stromal niche reshaping in B-cell lymphoma.
Project description:In this series we have analyzed the effect of donor age on the gene expression profile of mesenchymal stromal cells (alternatively named mesenchymal stem cells; MSC) from human bone marrow. Cells were taken from bone marrow aspirates from iliac crest (BM) of healthy donors or from the caput femoris (HIP) of elderly patients that received femoral head prosthesis.
Project description:Tumor cells can induce their own advantageous microenvironment. Here, we describe aberrant cathepsin S (CTSS) activity to modulate T-cell activation in follicular lymphoma (FL). In donor-derived FLs following bone marrow transplantation, we identified independent acquisition of CTSS mutations at Y132 in the donor´s and recipient's tumors. In a larger cohort, 6% of FL (20/312) harbored CTSS mutations, mostly Y132D, another 14% had CTSS amplification (40/280). Y132D leads to accelerated conversion from pro-CTSS to active CTSS and increased substrate cleavage, including CD74, which regulates MHC-II restricted antigen-presentation. In co-culture experiments, CTSS mutant lymphoma cells induced increased antigen-specific CD4+ T-cell activation. Moreover, antigen-processing was the top upregulated pathway in CTSS mutant primary FL biopsies. Thus, aberrant CTSS activity is a promising target in lymphoma.
Project description:Tumor infiltrating neutrophils (TAN) have been shown to exert both pro- and anti-tumoral activities and their recruitment and polarization are triggered by tumor-derived signals. Resident mesenchymal stromal cells (MSC) could contribute to tumor-supportive cell niche and have been shown to display tumor-specific transcriptomic, phenotypic, and functional features compared to normal tissue. In our study, we investigate whether these two cell subsets establish a bidirectional crosstalk in the context of B-cell lymphoma. We used microarrays to explore how neutrophils could trigger the polarization of tumor-supportive stromal cells. Gene expression analysis were performed on stromal cells (MSC) derived from bone marrow (BM) or tonsil (Resto) of healthy donors. These BM-MSC (n=3) or Resto (n=3) were primed or not with neutrophils for 1 day to induce stromal modification.