Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bone marrow micro-environment is a crucial player for myelomagenesis and disease progression.

ABSTRACT: Despite the advent of many therapeutic agents, such as bortezomib and lenalidomide that have significantly improved the overall survival, multiple myeloma remains an incurable disease. Failure to cure is multifactorial and can be attributed to the underlying genetic heterogeneity of the cancer and to the surrounding micro-environment. Understanding the mutual interaction between myeloma cells and micro-environment may lead to the development of novel treatment strategies able to eradicate this disease. In this review we discuss the principal molecules involved in the micro-environment network in multiple myeloma and the currently available therapies targeting them.

SUBMITTER: Mondello P

PROVIDER: S-EPMC5386771 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Bone marrow micro-environment is a crucial player for myelomagenesis and disease progression.

Mondello Patrizia P Cuzzocrea Salvatore S Navarra Michele M Mian Michael M

Oncotarget 20170301 12

Despite the advent of many therapeutic agents, such as bortezomib and lenalidomide that have significantly improved the overall survival, multiple myeloma remains an incurable disease. Failure to cure is multifactorial and can be attributed to the underlying genetic heterogeneity of the cancer and to the surrounding micro-environment. Understanding the mutual interaction between myeloma cells and micro-environment may lead to the development of novel treatment strategies able to eradicate this d ...[more]

PMID: 28099912

Similar Datasets

Progression of progenitor B cell leukemia is associated with alterations of the bone marrow micro-environment

Project description:Many of the clinical manifestations of B-lymphoid leukemia is a consequence of disrupted formation of normal blood cells. Upon diagnosis. the disease has often progressed into a state with a dramatic dominance of leukemic cells in the BM making it difficult to understand the environmental changes underlying the disruption in blood cell formation. To investigate this process in more detail we have explored pre-clinical stages of leukemia in a mouse model based on transplantation of B-ALL cells from mice trans-heterozygote for mutations in the Ebf1 and Pax5 genes to non-conditioned hosts. This revealed that while the recipient HSC compartment was relatively intact, the presence of erythroid progenitors and in more advanced disease, lymphoid progenitors was reduced. Progression of disease was also reflected in changes of the cellular composition of non hematopoietic compartments as well as changes in gene expression patterns in specific cellular subpopulations. This included increased expression of the cytokine Il7 in the mature stroma cell compartments. The relevance for Il7 in tumor progression was evident from the finding that leukemia development was delayed when tumor cells were transplanted to Il7 deficient mice. Our data suggest that progressive development of B-ALL primarily target the production of normal progenitor cells and that the micro-environment undergo changes that can be predicted to result in a more permissive environment for tumor growth.

2019-07-31 | GSE118964 | GEO

Bone marrow micro-environment mediated drug resistance in Acute promyelocytic leukemia

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 Î¼mol; 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

Bone marrow micro-environment mediated drug resistance in Acute promyelocytic leukemia

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

Glucose partitioning in the bone marrow micro-environment in acute myeloid leukaemia

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-04-13 | GSE227584 | GEO

Bone marrow microenvironment and tumor progression.

Project description:The bone marrow constitutes an unique microenvironment for cancer cells in three specific aspects. First, the bone marrow actively recruits circulating tumor cells where they find a sanctuary rich in growth factors and cytokines that promote their proliferation and survival. When in the bone marrow, tumor cells profoundly affect the homeostasis of the bone and the balance between osteogenesis and osteolysis. As a consequence, growth and survival factors normally sequestered into the bone matrix are released, further fueling cancer progression. Second, tumor cells actively recruit bone marrow-derived precursor cells into their own microenvironment. When in the tumors, these bone marrow-derived cells contribute to an inflammatory reaction and to the formation of the tumor vasculature. Third, bone marrow-derived cells can home in distant organs, where they form niches that attract circulating tumor cells. Our understanding of the contribution of the bone marrow microenvironment to cancer progression has therefore dramatically improved over the last few years. The importance of this new knowledge cannot be underestimated considering that the vast majority of cancer treatments such as cytotoxic and myeloablative chemotherapy, bone marrow transplantation and radiation therapy inflict a trauma to the bone marrow microenvironment. How such trauma affects the influence that the bone marrow microenvironment exerts on cancer is still poorly understood. In this article, the reciprocal relationship between the bone marrow microenvironment and tumor cells is reviewed, and its potential impact on cancer therapy is discussed.

| S-EPMC2654350 | biostudies-other

Glucose partitioning in the bone marrow micro-environment in acute myeloid leukaemia [bulk RNA-seq]

Project description:We used a positron emission tomography (PET) tracer 18F fluorodeoxyglucose ([18F]-FDG) and transcriptomic analysis to detect glucose uptake by cells in the bone marrow micro-environment with an MLL-AF9-induced mouse model. Leukaemic cells had the greatest glucose uptake. To determine whether glucose uptake is driven by intrinsic demand, we applied RNA-seq of sorted leukaemia cells (GFP+) and bone marrow micro-environment myeloid cells (GFP-CD11b+) from the MLL-AF9 transduced mouse model.

2023-04-14 | GSE227581 | GEO

Bone Marrow-Derived GCA<sup>+</sup> Immune Cells Drive Alzheimer's Disease Progression.

Project description:Alzheimer's disease (AD) is an age-related degenerative disease of the central nervous system (CNS), whereas the role of bone marrow immune cells in the pathogenesis of AD remains unclear. Here, the study reveals that compared to matched healthy individuals, AD patients have higher circulating grancalcin (GCA) levels, which negatively correlate with cognitive function. Bone marrow-derived GCA+ immune cells, which secret abundant GCA and increase during aging, preferentially invaded the hippocampus and cortex of AD mouse model in a C-C Motif Chemokine Receptor 10 (CCR10)-dependent manner. Transplanting GCA+ immune cells or direct stereotaxic injection of recombinant GCA protein intensified amyloid plaque load and aggravated cognitive and memory impairments. In contrast, genetic ablation of GCA in the hematopoietic compartment improves cognitive and memory function. Mechanistically, GCA competitively binds to the low-density lipoprotein receptor-related protein 1 (LRP1) in microglia, thus inhibiting phagocytosis and clearance of Aβ and potentiating neuropathological changes. Importantly, GCA-neutralizing antibody treatment rejuvenated cognitive and memory function and constrained AD progression. Together, the study demonstrates a pathological role of GCA+ immune cells instigating cognitive and memory decline, suggesting that GCA+ immune cells can be a potential target for innovative therapeutic strategies in AD.

| S-EPMC10754099 | biostudies-literature

Glucose partitioning in the bone marrow micro-environment in acute myeloid leukaemia [single-cell RNA-seq]

Project description:To identify the metabolic transcriptome landscape within leukaemic cells we performed scRNA-Seq on the sorted leukaemia cells (GFP+) cells from MLL-AF9 mice.

2023-04-14 | GSE227583 | GEO

Crucial role of the local micro-environment in fate decision of neonatal rat NG2 progenitors.

Project description:ObjectivesThe fate choice of neural progenitor cells could be dictated by local cellular environment of the adult CNS. The aim of our study was to investigate the effect of hippocampal tissue on differentiation and maturation of oligodendrocyte NG2 precursor cells.Materials and methodsHippocampal slice culture was established from the brains of 7-day-old rats. NG2 precursor cells, obtained from a 12-day-old mixed primary culture of neonatal rat cerebral hemispheres, were labelled with chloromethyl-fluorescein-diacetete and seeded on the hippocampal slices. After 7-14 days in co-culture, cells were stained with neural markers.ResultsNG2 cells differentiated predominantly into oligodendrocytes, presenting various stages of maturation: progenitors (NG2), pre-oligodendrocytes (O4) and finally mature GalC-positive cells. However, except for a few cells with astrocyte-specific S100b staining, a considerable number of these cells differentiated into neurons: TUJ(+) and even MAP-2(+) cells were frequently observed. Moreover, a certain population of these cells preserved proliferative properties of primary precursor cells, as revealed by Ki67 expression.ConclusionsThe neuronal micro-environment provided by the culture of hippocampal slices is potent for induction of neurogenesis from oligodendrocyte NG2(+)/PDGFRalpha(+)/CNP(+) progenitor cells and promotes their differentiation not only into macroglia but also into neurons. It also sustains their proliferative capacity. The results indicate the crucial role of the local cellular environment in fate decision of primary NG2(+) multipotent neural progenitor cells, which may affect their behaviour after transplantation into the central nervous system.

| S-EPMC6496871 | biostudies-literature