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Bone marrow microenvironment

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https://www.readbyqxmd.com/read/29783691/old-and-young-actors-playing-novel-roles-in-the-drama-of-multiple-myeloma-bone-marrow-microenvironment-dependent-drug-resistance
#1
REVIEW
Sabrina Manni, Marilena Carrino, Gianpietro Semenzato, Francesco Piazza
Multiple myeloma (MM) is the second most frequent hematologic cancer. In addition to the deleterious effects of neoplastic plasma cell growth and spreading during the disease evolution, this tumor is characterized by the serious pathological consequences due to the massive secretion of monoclonal immunoglobulins and by the derangement of bone physiology with progressive weakening of the skeleton. Despite significant progresses having been made in the last two decades in the therapeutic management of this plasma cell tumor, MM remains invariably lethal, due to its extremely complex genetic architecture and to the constant protection it receives from the tumor niche, which is represented by the bone marrow microenvironment...
May 18, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29782940/defining-osteoblast-and-adipocyte-lineages-in-the-bone-marrow
#2
J L Pierce, D L Begun, J J Westendorf, M E McGee-Lawrence
Bone is a complex endocrine organ that facilitates structural support, protection to vital organs, sites for hematopoiesis, and calcium homeostasis. The bone marrow microenvironment is a heterogeneous niche consisting of multipotent musculoskeletal and hematopoietic progenitors and their derivative terminal cell types. Amongst these progenitors, bone marrow mesenchymal stem/stromal cells (BMSCs) may differentiate into osteogenic, adipogenic, myogenic, and chondrogenic lineages to support musculoskeletal development as well as tissue homeostasis, regeneration and repair during adulthood...
May 18, 2018: Bone
https://www.readbyqxmd.com/read/29778716/the-hematopoietic-stem-cell-niche-what-s-so-special-about-bone
#3
REVIEW
Benjamin J Frisch
Hematopoietic stem cells (HSCs) require a supportive microenvironment to regulate their function and produce sufficient hematopoietic cells over the lifetime of an individual. With the exception of fish, all vertebrates, including mammals, maintain HSCs in a complex niche within the bone marrow. Several bone specific cellular populations have been implicated as components of the HSC niche and are part of a complex network that regulates HSC functions. However, the full extent of interactions within the HSC niche, and the role of individual cell populations remain to be fully elucidated...
May 17, 2018: Bone
https://www.readbyqxmd.com/read/29776381/wnt-signaling-in-multiple-myeloma-a-central-player-in-disease-with-therapeutic-potential
#4
REVIEW
Ingrid Spaan, Reinier A Raymakers, Anja van de Stolpe, Victor Peperzak
Multiple myeloma is the second most frequent hematological malignancy in the western world and remains incurable, predominantly due to acquired drug resistance and disease relapse. The highly conserved Wnt signal transduction pathway, which plays a key role in regulating cellular processes of proliferation, differentiation, migration, and stem cell self-renewal, is associated with multiple aspects of disease. Bone homeostasis is severely disturbed by Wnt antagonists that are secreted by the malignant plasma cells in the bone marrow...
May 18, 2018: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/29773599/tgf%C3%AE-1-mediated-functional-inhibition-of-mesenchymal-stromal-cells-in-myelodysplastic-syndromes-and-acute-myeloid-leukemia
#5
Stefanie Geyh, Manuel Rodríguez-Paredes, Paul Jäger, Annemarie Koch, Felix Bormann, Julian Gutekunst, Christoph Zilkens, Ulrich Germing, Guido Kobbe, Frank Lyko, Rainer Haas, Thomas Schroeder
Mesenchymal stromal cells are involved in the pathogenesis of myelodysplastic syndromes and acute myeloid leukemia, but the underlying mechanisms are incompletely understood. To further characterize the pathological phenotype we performed RNA sequencing of mesenchymal stromal cells from patients with myelodysplastic syndromes and acute myeloid leukemia revealing a specific molecular signature of genes commonly deregulated in myelodysplastic syndromes and acute myeloid leukemia. Pathway analysis showed a strong enrichment of genes related to osteogenesis, senescence, inflammation and inhibitory cytokines thereby reflecting the structural and functional deficits of mesenchymal stromal cells in myelodysplastic syndromes and acute myeloid leukemia on a molecular level...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29773597/hematopoietic-stem-cell-loss-and-hematopoietic-failure-in-severe-aplastic-anemia-is-driven-by-macrophages-and-aberrant-podoplanin-expression
#6
Amanda McCabe, Julianne N P Smith, Angelica Costello, Jackson Maloney, Divya Katikaneni, Katherine C MacNamara
Severe aplastic anemia results from profound hematopoietic stem cell loss. T cells and interferon gamma have long been associated with severe aplastic anemia, yet the underlying mechanisms driving hematopoietic stem cell loss remain unknown. Using a mouse model of severe aplastic anemia, we demonstrate that interferon gamma-dependent hematopoietic stem cell loss required macrophages. Interferon gamma was necessary for bone marrow macrophage persistence, despite loss of other myeloid cells and hematopoietic stem cells...
May 17, 2018: Haematologica
https://www.readbyqxmd.com/read/29769543/the-cytokine-secretion-profile-of-mesenchymal-stromal-cells-is-determined-by-surface-structure-of-the-microenvironment
#7
Daniëlle G Leuning, Nick R M Beijer, Nadia A du Fossé, Steven Vermeulen, Ellen Lievers, Cees van Kooten, Ton J Rabelink, Jan de Boer
Mesenchymal stromal cells (MSC) secrete factors that contribute to organ homeostasis and repair in a tissue specific manner. For instance, kidney perivascular mesenchymal stromal cells (kPSCs) can facilitate renal epithelial repair through secretion of hepatocyte growth factor (HGF) while the secretome of bone marrow MSCs gives rise to immunosuppression. Stromal cells function in a complex 3-dimensional (3D) connective tissue architecture that induces conformational adaptation. Here we tested the hypothesis that surface topography and associated cell adaptations dictate stromal cell function through tuning of the cytokines released...
May 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29767235/inhibition-of-microrna%C3%A2-16-protects-mesenchymal-stem-cells-against-apoptosis
#8
Jiang Rui, Shaohong Fang, Yongchen Wang, Bo Lv, Bo Yu, Shufeng Li
Bone marrow‑derived mesenchymal stem cells (BM‑MSCs) have been used in experimental research and clinical trials for heart function restoration and cardiomyocyte regeneration. However, due to a hostile microenvironment created by ischemia, hypoxia and pro‑inflammatory factors, the survival rate of implanted BM‑MSCs remains low. Therefore, strategies that can promote BM‑MSC survival and prevent apoptosis are required. Previous studies have reported that microRNA‑16 (miR‑16) can inhibit cell proliferation by targeting several proteins and signal pathway, not only by inducing apoptosis...
May 11, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29765406/the-differentiation-balance-of-bone-marrow-mesenchymal-stem-cells-is-crucial-to-hematopoiesis
#9
REVIEW
Jiang Wu, Weiwei Zhang, Qian Ran, Yang Xiang, Jiang F Zhong, Shengwen Calvin Li, Zhongjun Li
Bone marrow mesenchymal stem cells (BMSCs), the important component and regulator of bone marrow microenvironment, give rise to hematopoietic-supporting stromal cells and form hematopoietic niches for hematopoietic stem cells (HSCs). However, how BMSC differentiation affects hematopoiesis is poorly understood. In this review, we focus on the role of BMSC differentiation in hematopoiesis. We discussed the role of BMSCs and their progeny in hematopoiesis. We also examine the mechanisms that cause differentiation bias of BMSCs in stress conditions including aging, irradiation, and chemotherapy...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29765356/soluble-and-cell-cell-mediated-drivers-of-proteasome-inhibitor-resistance-in-multiple-myeloma
#10
REVIEW
Mariah L Farrell, Michaela R Reagan
It is becoming clear that myeloma cell-induced disruption of the highly organized bone marrow components (both cellular and extracellular) results in destruction of the marrow and support for multiple myeloma (MM) cell proliferation, survival, migration, and drug resistance. Since the first phase I clinical trial on bortezomib was published 15 years ago, proteasome inhibitors (PIs) have become increasingly common for treatment of MM and are currently an essential part of any anti-myeloma combination therapy...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29759563/targeting-the-tumor-promoting-effects-of-adenosine-in-chronic-lymphocytic-leukemia
#11
REVIEW
Yiqing Cai, Lili Feng, Xin Wang
Chronic lymphocytic leukemia (CLL) is a hematological malignancy which is characterized by progressive accumulation of functionally deficient B cells in blood, bone marrow, and lymphatic tissue. The tumor microenvironment (TME) appears to play a critical role in genesis and progression of CLL. High levels of extracellular adenosine (ADO) are detected in CLL as a consequence of expression of ecto-enzymes, such as CD39 and CD73. Extracellular ADO exhibits a broad range of effects on cell cycle control, immunoregulation, angiogenesis and cytokine regulation through both direct and indirect mechanisms...
June 2018: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/29753837/status-of-nk-cell-recovery-in-day-21-bone-marrow-after-allogeneic-hematopoietic-stem-cell-transplantation-predicts-clinical-outcome
#12
Norimichi Hattori, Bungo Saito, Yohei Sasaki, Shotaro Shimada, So Murai, Maasa Abe, Yuta Baba, Megumi Watanuki, Shun Fujiwara, Yukiko Kawaguchi, Nana Arai, Nobuyuki Kabasawa, Hiroyuki Tsukamoto, Yui Uto, Hirotsugu Ariizumi, Kouji Yanagisawa, Hiroshi Harada, Tsuyoshi Nakamaki
Rapid immune recovery following allogeneic hematopoietic stem cell transplantation (allo-HSCT) is important for clinical outcome prediction. In most studies, immune recovery after allo-HSCT has been monitored via peripheral blood. However, few reports regarding the status of absolute lymphocyte subsets in the bone marrow (BM) microenvironment have been undertaken. Therefore, we evaluated the clinical impact of immune recovery in the early period following allo-HSCT using BM samples. We showed that delayed natural killer (NK) cell recovery was independently associated with a poor prognosis for overall survival (hazard ratio (HR), 3...
May 10, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29753718/early-tgf-%C3%AE-inhibition-in-mice-reduces-the-incidence-of-breast-cancer-induced-bone-disease-in-a-myeloid-dependent-manner
#13
Denise Buenrostro, Kristin A Kwakwa, Nicole E Putnam, Alyssa R Merkel, Joshua R Johnson, James E Cassat, Julie A Sterling
The tumor-cell microenvironment is recognized as a dynamic place where critical cell interactions occur and play an important role in altering tumorigenesis. While many studies have investigated the effects of cellular cross-talk within distinct tumor microenvironments, these interactions have yet to be fully examined in bone. It is well-established that many common cancers metastasize to bone, resulting in the development of tumor-induced bone disease (TIBD), a multi-facetted illness that is driven by complex cell interactions within the bone marrow...
May 10, 2018: Bone
https://www.readbyqxmd.com/read/29752311/myeloid-derived-suppressor-cells-impair-b-cell-responses-in-lung-cancer-through-il-7-and-stat5
#14
Yong Wang, Cara C Schafer, Kenneth P Hough, Sultan Tousif, Steven R Duncan, John F Kearney, Selvarangan Ponnazhagan, Hui-Chen Hsu, Jessy S Deshane
Myeloid-derived suppressor cells (MDSCs) are known suppressors of antitumor immunity, affecting amino acid metabolism and T cell function in the tumor microenvironment. However, it is unknown whether MDSCs regulate B cell responses during tumor progression. Using a syngeneic mouse model of lung cancer, we show reduction in percentages and absolute numbers of B cell subsets including pro-, pre-, and mature B cells in the bone marrow (BM) of tumor-bearing mice. The kinetics of this impaired B cell response correlated with the progressive infiltration of MDSCs...
May 11, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29749549/enhanced-proliferation-and-differentiation-of-ho-1-gene-modified-bone-marrow-derived-mesenchymal-stem-cells-in-the-acute-injured-kidney
#15
Nanmei Liu, Huiling Wang, Guofeng Han, Jin Cheng, Weifeng Hu, Jinyuan Zhang
The aim of the present study was to investigate the effect of heme oxygenase-1 (HO-1) overexpression on the survival and differentiation ability of bone marrow‑derived mesenchymal stem cells (BMSCs) in the acute kidney injury (AKI) microenvironment. HO-1-BMSCs and enhanced green fluorescent protein (eGFP)-BMSCs were constructed. Rat ischemia/reperfusion (I/R)‑AKI-kidney homogenate supernatant was prep-ared to treat the BMSCs, eGFP-BMSCs and HO-1-BMSCs in vitro. In the AKI microenvironment, the HO-1-BMSCs exhibited a smaller proportion of cells at the G0/G1 phase, and a larger proportion of cells expressing proliferating cell nuclear antigen (PCNA) and cytokeratin 18 (CK18)...
May 11, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29748955/investigational-agents-in-immunotherapy-a-new-horizon-for-the-treatment-of-multiple-myeloma
#16
REVIEW
Cindy Varga, Jacob P Laubach, Kenneth C Anderson, Paul G Richardson
The treatment of multiple myeloma (MM) has gone through several major advances over the last 5 years with the introduction of next generation proteasome inhibitors (PI; carfilzomib, ixazomib) and immunomodulatory derivatives (IMiD; pomalidomide), with these new agents having a substantial impact on patient outcome. However, despite these advances, MM remains a highly resistant disease given its propensity for clonal heterogeneity and its complex interaction with the surrounding bone marrow microenvironment...
May 10, 2018: British Journal of Haematology
https://www.readbyqxmd.com/read/29747461/role-of-the-bone-microenvironment-in-the-development-of-painful-complications-of-skeletal-metastases
#17
REVIEW
Sun H Park, Matthew R Eber, D Brooke Widner, Yusuke Shiozawa
Cancer-induced bone pain (CIBP) is the most common and painful complication in patients with bone metastases. It causes a significant reduction in patient quality of life. Available analgesic treatments for CIBP, such as opioids that target the central nervous system, come with severe side effects as well as the risk of abuse and addiction. Therefore, alternative treatments for CIBP are desperately needed. Although the exact mechanisms of CIBP have not been fully elucidated, recent studies using preclinical models have demonstrated the role of the bone marrow microenvironment (e...
May 10, 2018: Cancers
https://www.readbyqxmd.com/read/29745272/extracellular-vesicles-in-hematological-malignancies
#18
Zofia Litwińska, Karolina Łuczkowska, Bogusław Machaliński
Extracellular vesicles (EVs) act as transporters that carry regulatory molecules between cells in physiologic and pathologic states; therefore, they play a crucial role in thrombosis, inflammation, angiogenesis, vascular dysfunction and other processes that affect the course of hematologic diseases. Within the tumor microenvironment, for example the leukemic bone marrow, EVs-mediated signaling may direct the activities of surrounding cells and act as a positive feedback loop that contributes to cancer progression...
May 10, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29742289/the-genetic-and-molecular-pathogenesis-of-myelodysplastic-syndromes
#19
REVIEW
Rory M Shallis, Rami Ahmad, Amer M Zeidan
Myelodysplastic syndromes (MDS) comprise a diverse group of clonal and malignant myeloid disorders characterized by ineffective hematopoiesis, resultant peripheral cytopenias, and a meaningful increased risk of progression to acute myeloid leukemia. A wide array of recurring genetic mutations involved in RNA splicing, histone manipulation, DNA methylation, transcription factors, kinase signaling, DNA repair, cohesin proteins, and other signal transduction elements have been identified as important substrates for the development of MDS...
May 9, 2018: European Journal of Haematology
https://www.readbyqxmd.com/read/29740536/regulation-of-malignant-hematopoiesis-by-bone-marrow-microenvironment
#20
REVIEW
Noboru Asada
Hematopoietic stem cells (HSCs) that give rise to all kinds of hematopoietic lineage cells on various demands throughout life are maintained in a specialized microenvironment called "niche" in the bone marrow (BM). Defining niche cells and unveiling its function have been the subject of intense study, and it is becoming increasingly clear how niche cells regulate HSCs in normal hematopoiesis. Leukemia stem cells (LSCs), which are able to produce leukemic cells and maintain leukemic clones, are assumed to share common features with healthy HSCs...
2018: Frontiers in Oncology
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