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https://www.readbyqxmd.com/read/28923207/eviction-from-the-sanctuary-development-of-targeted-therapy-against-cell-adhesion-molecules-in-acute-lymphoblastic-leukemia
#1
REVIEW
Sonali P Barwe, Anthony Quagliano, Anilkumar Gopalakrishnapillai
Acute lymphoblastic leukemia (ALL) is a malignant hematological disease afflicting hematopoiesis in the bone marrow. While 80%-90% of patients diagnosed with ALL will achieve complete remission at some point during treatment, ALL is associated with high relapse rate, with a 5-year overall survival rate of 68%. The initial remission failure and the high rate of relapse can be attributed to intrinsic chemoprotective mechanisms that allow persistence of ALL cells despite therapy. These mechanisms are mediated, at least in part, through the engagement of cell adhesion molecules (CAMs) within the bone marrow microenvironment...
April 2017: Seminars in Oncology
https://www.readbyqxmd.com/read/28910419/il-10-mediated-signals-act-as-a-switch-for-lymphoproliferation-in-human-t-cell-leukemia-virus-type-1-infection-by-activating-the-stat3-and-irf4-pathways
#2
Leila Sawada, Yoshiko Nagano, Atsuhiko Hasegawa, Hikari Kanai, Kai Nogami, Sayaka Ito, Tomoo Sato, Yoshihisa Yamano, Yuetsu Tanaka, Takao Masuda, Mari Kannagi
Human T-cell leukemia virus type-1 (HTLV-1) causes two distinct diseases, adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Since there are no disease-specific differences among HTLV-1 strains, the etiological mechanisms separating these respective lymphoproliferative and inflammatory diseases are not well understood. In this study, by using IL-2-dependent HTLV-1-infected T-cell lines (ILTs) established from patients with ATL and HAM/TSP, we demonstrate that the anti-inflammatory cytokine IL-10 and its downstream signals potentially act as a switch for proliferation in HTLV-1-infected cells...
September 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28888743/htlv-1-infected-thymic-epithelial-cells-convey-the-virus-to-cd4-t-lymphocytes
#3
Luciana Rodrigues Carvalho Barros, Leandra Linhares-Lacerda, Klaysa Moreira-Ramos, Marcelo Ribeiro-Alves, Maria Cristina Machado Motta, Dumith Chequer Bou-Habib, Wilson Savino
The human T-lymphotropic virus type-1 (HTLV-1) is the causative agent of adult T cell leukemia/lymphoma (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). CD4(+)T cells are the main target of HTLV-1, but other cell types are known to be infected, including immature lymphocytes. Developing T cells undergo differentiation in the thymus, through migration and interaction with the thymic microenvironment, in particular with thymic epithelial cells (TEC) the major component of this three dimensional meshwork of non-lymphoid cells...
August 14, 2017: Immunobiology
https://www.readbyqxmd.com/read/28884706/biological-features-of-bone-marrow-mesenchymal-stromal-cells-in-childhood-acute-lymphoblastic-leukemia
#4
Stella Genitsari, Eftichia Stiakaki, Chryssoula Perdikogianni, Georgia Martimianaki, Iordanis Pelagiadis, Margarita Pesmatzoglou, Maria Kalmanti, Helen Dimitriou
OBJECTIVE: Mesenchymal Stromal Cells (MSC) have a supportive role in hematopoiesis and as components of the bone marrow microenvironment may present alterations during ALL and be affected by chemotherapeutic agents. We examined the biological and functional characteristics of MSC at ALL diagnosis and treatment and their effect on MSC qualitative properties. MATERIALS AND METHODS: Immunophenotypic characterization, evaluation of clonogenicity and proliferative capacity were performed...
September 8, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28882083/regulation-of-mapk-signaling-and-implications-in-chronic-lymphocytic-leukemia
#5
Ashima Shukla, Vipul Shukla, Shantaram S Joshi
Chronic lymphocytic leukemia (CLL) is a heterogeneous B cell malignancy that still remains incurable. Recent studies have highlighted cellular and non-cellular components of the tissue microenvironment in CLL that help nurture the growth of leukemic cells by providing the necessary stimuli for their proliferation and survival. The diverse stimuli in the specialized tissue microenvironment of CLL lead to constitutive activation of several signaling pathways that includes B cell receptor signaling and the associated mitogen-activated protein kinase (MAPK) signaling...
September 7, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28881725/nurse-like-cells-promote-cll-survival-through-lfa-3-cd2-interactions
#6
Frédéric Boissard, Marie Tosolini, Laetitia Ligat, Anne Quillet-Mary, Frederic Lopez, Jean-Jacques Fournié, Loic Ysebaert, Mary Poupot
In the tumoral micro-environment (TME) of chronic lymphocytic leukemia (CLL), nurse-like cells (NLC) are tumor-associated macrophages which play a critical role in the survival and chemoresistance of tumoral cells. This pro-survival activity is known to involve soluble factors, but few data are available on the relative role of cells cross-talk. Here, we used a transcriptome-based approach to systematically investigate the expression of various receptor/ligand pairs at the surface of NLC/CLL cells. Their relative contribution to CLL survival was assessed both by fluorescent microscopy to identify cellular interactions and by the use of functional tests to measure the impact of uncoupling these pairs with blocking monoclonal antibodies...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28870867/hematologic-neoplasms-dendritic-cells-vaccines-in-motion
#7
REVIEW
Domenico Galati, Serena Zanotta
Dendritic cells (DCs) are bone-marrow-derived immune cells accounted for a key role in cancer vaccination as potent antigen-presenting cells within the immune system. Cancer microenvironment can modulate DCs maturation resulting in their accumulation into functional states associated with a reduced antitumor immune response. In this regard, a successful cancer vaccine needs to mount a potent antitumor immune response able to overcome the immunosuppressive tumor milieu. As a consequence, DCs-based approaches are a safe and promising strategy for improving the therapeutic efficacy in hematological malignancies, particularly in combinations with additional treatments...
September 11, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28870739/increased-vascular-permeability-in-the-bone-marrow-microenvironment-contributes-to-disease-progression-and-drug-response-in-acute-myeloid-leukemia
#8
Diana Passaro, Alessandro Di Tullio, Ander Abarrategi, Kevin Rouault-Pierre, Katie Foster, Linda Ariza-McNaughton, Beatriz Montaner, Probir Chakravarty, Leena Bhaw, Giovanni Diana, François Lassailly, John Gribben, Dominique Bonnet
The biological and clinical behaviors of hematological malignancies can be influenced by the active crosstalk with an altered bone marrow (BM) microenvironment. In the present study, we provide a detailed picture of the BM vasculature in acute myeloid leukemia using intravital two-photon microscopy. We found several abnormalities in the vascular architecture and function in patient-derived xenografts (PDX), such as vascular leakiness and increased hypoxia. Transcriptomic analysis in endothelial cells identified nitric oxide (NO) as major mediator of this phenotype in PDX and in patient-derived biopsies...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28863345/the-stromal-microenvironment-modulates-mitochondrial-oxidative-phosphorylation-in-chronic-lymphocytic-leukemia-cells
#9
Hima V Vangapandu, Mary L Ayres, Christopher A Bristow, William G Wierda, Michael J Keating, Kumudha Balakrishnan, Christine M Stellrecht, Varsha Gandhi
Peripheral blood chronic lymphocytic leukemia (CLL) cells are replicationally quiescent mature B-cells. In short-term cultures, supporting stromal cells provide a survival advantage to CLL cells by inducing transcription and translation without promoting proliferation. We hypothesized that the stromal microenvironment augments malignant B cells' metabolism to enable the cells to cope with their energy demands for transcription and translation. We used extracellular flux analysis to assess the two major energy-generating pathways, mitochondrial oxidative phosphorylation (OxPhos) and glycolysis, in primary CLL cells in the presence of three different stromal cell lines...
August 29, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28838991/syk-inhibition-thwarts-the-baff-b-cell-receptor-crosstalk-and-thereby-antagonizes-mcl-1-in-chronic-lymphocytic-leukemia
#10
Cody Paiva, Taylor A Rowland, Bhargava Sreekantham, Claire Godbersen, Scott R Best, Prabhjot Kaur, Marc M Loriaux, Stephen E F Spurgeon, Olga V Danilova, Alexey V Danilov
Although small molecule inhibitors of B-cell receptor-associated kinases revolutionized therapy in chronic lymphocytic leukemia, they provide for incomplete responses. Pro-survival signaling emanating from the microenvironment may foster therapeutic resistance of the malignant B-cells resident in the protective lymphoid niches. BAFF is critical in survival of both healthy and neoplastic B-cells. However, the pro-survival pathways triggered by BAFF have not been fully characterized. Here we show that BAFF elicited resistance to spontaneous and drug-induced apoptosis in stromal co-cultures, induced activation of both canonical and non-canonical NFκB signaling pathways and triggered B-cell receptor signaling in chronic lymphocytic leukemia cells, independent of IGHV mutational status...
August 24, 2017: Haematologica
https://www.readbyqxmd.com/read/28829353/chemokines-as-a-conductor-of-bone-marrow-microenvironment-in-chronic-myeloid-leukemia
#11
REVIEW
Naofumi Mukaida, Yamato Tanabe, Tomohisa Baba
All blood lineage cells are generated from hematopoietic stem cells (HSCs), which reside in bone marrow after birth. HSCs self-renew, proliferate, and differentiate into mature progeny under the control of local microenvironments including hematopoietic niche, which can deliver regulatory signals in the form of bound or secreted molecules and from physical cues such as oxygen tension and shear stress. Among these mediators, accumulating evidence indicates the potential involvement of several chemokines, particularly CXCL12, in the interaction between HSCs and bone marrow microenvironments...
August 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28826860/the-microenvironment-in-myelodysplastic-syndromes-niche-mediated-disease-initiation-and-progression
#12
REVIEW
Allison J Li, Laura M Calvi
Myelodysplastic syndromes (MDS) are clonal disorders of hematopoietic stem and progenitor cells and represent the most common cause of acquired marrow failure. Hallmarked by ineffective hematopoiesis, dysplastic marrow, and risk of transformation to acute leukemia, MDS remains a poorly treated disease. Although identification of hematopoietic aberrations in human MDS has contributed significantly to our understanding of MDS pathogenesis, evidence now identify the bone marrow microenvironment (BMME) as another key contributor to disease initiation and progression...
August 18, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28819278/interleukin-4-induces-apoptosis-of-acute-myeloid-leukemia-cells-in-a-stat6-dependent-manner
#13
P Peña-Martínez, M Eriksson, R Ramakrishnan, M Chapellier, C Högberg, C Orsmark-Pietras, J Richter, A Andersson, T Fioretos, M Järås
Cytokines provide signals that regulate immature normal and acute myeloid leukemia (AML) cells in the bone marrow microenvironment. We here identify interleukin 4 (IL4) as a selective inhibitor of AML cell growth and survival in a cytokine screen using fluorescently labeled AML cells. RNA-sequencing of the AML cells revealed an IL4-induced upregulation of Stat6 target genes and enrichment of apoptosis-related gene expression signatures. Consistent with these findings, we found that IL4 stimulation of AML cells induced Stat6 phosphorylation and that disruption of Stat6 using CRISPR/Cas9-genetic engineering rendered cells partially resistant to IL4-induced apoptosis...
August 18, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28816238/acute-myeloid-leukemia-transforms-the-bone-marrow-niche-into-a-leukemia-permissive-microenvironment-through-exosome-secretion
#14
B Kumar, M Garcia, L Weng, X Jung, J L Murakami, X Hu, T McDonald, A Lin, A R Kumar, D L DiGiusto, A S Stein, V A Pullarkat, S K Hui, N Carlesso, Y-H Kuo, R Bhatia, G Marcucci, C-C Chen
Little is known about how leukemia cells alter the bone marrow (BM) niche to facilitate their own growth and evade chemotherapy. Here, we provide evidence that acute myeloid leukemia (AML) blasts remodel the BM niche into a leukemia growth-permissive and normal hematopoiesis-suppressive microenvironment through exosome secretion. Either engrafted AML cells or AML-derived exosomes increased mesenchymal stromal progenitors and blocked osteolineage development and bone formation in vivo. Preconditioning with AML-derived exosomes 'primed' the animals for accelerated AML growth...
August 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28815730/loss-of-bmi-1-dampens-migration-and-emt-of-colorectal-cancer-in-inflammatory-microenvironment-through-tlr4-md-2-myd88-mediated-nf-%C3%AE%C2%BAb-signaling
#15
Kai Ye, Qi-Wei Chen, Ya-Feng Sun, Jian-An Lin, Jian-Hua Xu
Increasing evidence from various clinical and experimental studies has demonstrated that the inflammatory microenvironment created by immune cells facilitates tumor migration. Epithelial-mesenchymal transition (EMT) is involved in the progression of cancer invasion and metastasis in an inflammatory microenvironment. B-lymphoma Moloney murine leukemia virus insertion region 1 (BMI-1) acts as an oncogene in various tumors. Ectopic expression of Bmi-1 have an effect on EMT and invasiveness. The purpose of this study was to investigate the efficacy of BMI-1 on inflammation-induced tumor migration and EMT and the underlying mechanism...
August 16, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28807161/phytochemical-modulation-of-apoptosis-and-autophagy-strategies-to-overcome-chemoresistance-in-leukemic-stem-cells-in-the-bone-marrow-microenvironment
#16
Helen C Owen, Sandra Appiah, Noor Hasan, Lucy Ghali, Ghada Elayat, Celia Bell
Advances in scientific research and targeted treatment regimes have improved survival rates for many cancers over the past few decades. However, for some types of leukemia, including acute lymphoblastic and acute myeloid leukemia, mortality rates have continued to rise, with chemoresistance in leukemic stem cells (LSCs) being a major contributing factor. Most cancer drug therapies act by inducing apoptosis in dividing cells but are ineffective in targeting quiescent LSCs. Niches in the bone marrow, known as leukemic niches, behave as "sanctuaries" where LSCs acquire drug resistance...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28802664/cytokines-and-soluble-hla-g-levels-in-bone-marrow-stroma-and-their-association-with-the-survival-rate-of-patients-exhibiting-childhood-t-cell-acute-lymphoblastic-leukemia
#17
Renata Dos Santos Almeida, Alessandra Maria de Luna Ramos, Carlos Feitosa Luna, Francisco Pedrosa, Eduardo Antônio Donadi, Norma Lucena-Silva
Leukemic cells can induce defective expression of soluble factors and change marrow cytokine profile, leading to aberrant cell signaling, cell fixation and cell proliferation in bone marrow. T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disorder which accounts for 15% of pediatric ALL. To evaluate the contribution of immunological factors on T-ALL survival, we measured Th1, Th2, Th17 cytokines and soluble HLA-G (sHLA-G) levels in bone marrow from 32 Brazilian children at diagnosis (D0), after induction (D19) and after consolidation (D49) of the chemotherapy phase...
August 9, 2017: Cytokine
https://www.readbyqxmd.com/read/28775118/chronic-lymphocytic-leukemia-cells-are-active-participants-in-microenvironmental-cross-talk
#18
Martijn Ha van Attekum, Eric Eldering, Arnon P Kater
The importance of the tumor microenvironment in chronic lymphocytic leukemia is widely accepted. Yet, the understanding of the complex interplay between the various types of bystander cells and chronic lymphocytic leukemia cells is incomplete. Whereas numerous studies have indicated that bystander cells provide chronic lymphocytic leukemia-supportive functions, it has also become clear that chronic lymphocytic leukemia cells actively engage in the formation of a supportive tumor microenvironment by engaging in several cross-talk mechanisms...
August 3, 2017: Haematologica
https://www.readbyqxmd.com/read/28767666/mismatch-repair-deficient-hematopoietic-stem-cells-are-preleukemic-stem-cells
#19
Yulan Qing, Stanton L Gerson
Whereas transformation events in hematopoietic malignancies may occur at different developmental stages, the initial mutation originates in hematopoietic stem cells (HSCs), creating a preleukemic stem cell (PLSC). Subsequent mutations at either stem cell or progenitor cell levels transform the PLSC into lymphoma/leukemia initiating cells (LIC). Thymic lymphomas have been thought to develop from developing thymocytes. T cell progenitors are generated from HSCs in the bone marrow (BM), but maturation and proliferation of T cells as well as T-lymphomagenesis depends on both regulatory mechanisms and microenvironment within the thymus...
2017: PloS One
https://www.readbyqxmd.com/read/28758974/immunotherapeutic-concepts-to-target-acute-myeloid-leukemia-focusing-on-the-role-of-monoclonal-antibodies-hypomethylating-agents-and-the-leukemic-microenvironment
#20
REVIEW
Olumide Babajide Gbolahan, Amer M Zeidan, Maximilian Stahl, Mohammad Abu Zaid, Sherif Farag, Sophie Paczesny, Heiko Konig
Intensive chemotherapeutic protocols and allogeneic stem cell transplantation continue to represent the mainstay of acute myeloid leukemia (AML) treatment. Although this approach leads to remissions in the majority of patients, long-term disease control remains unsatisfactory as mirrored by overall survival rates of approximately 30%. The reason for this poor outcome is, in part, due to various toxicities associated with traditional AML therapy and the limited ability of most patients to tolerate such treatment...
July 31, 2017: International Journal of Molecular Sciences
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