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leukemia MicroEnvironment

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https://www.readbyqxmd.com/read/29156850/harness-the-synergy-between-targeted-therapy-and-immunotherapy-what-have-we-learned-and-where-are-we-headed
#1
REVIEW
Xiaoyan Liu, Qing Zhou, Yan Xu, Minjiang Chen, Jing Zhao, Mengzhao Wang
Since the introduction of imatinib for the treatment of chronic myelogenous leukemia, several oncogenic mutations have been identified in various malignancies that can serve as targets for therapy. More recently, a deeper insight into the mechanism of antitumor immunity and tumor immunoevasion have facilitated the development of novel immunotherapy agents. Certain targeted agents have the ability of inhibiting tumor growth without causing severe lymphocytopenia and amplifying antitumor immune response by increasing tumor antigenicity, enhancing intratumoral T cell infiltration, and altering the tumor immune microenvironment, which provides a rationale for combining targeted therapy with immunotherapy...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29154208/characteristics-of-nk-cells-from-leukemic-microenvironment-in-mll-af9-induced-acute-myeloid-leukemia
#2
Feifei Yang, Rong Wang, Wenli Feng, Chong Chen, Xiao Yang, Lina Wang, Yuting Hu, Qian Ren, Guoguang Zheng
NK cells are indispensable components of tissue microenvironment and play vital in both innate and adaptive immunity. The activation and function of NK cells are affected by tumor microenvironments. NK cells are also important players in leukemic microenvironment. However, their characteristics in leukemic microenvironment, including maturation status, phenotype, subpopulations and functional roles especially immunoregulatory potential, have not been well established. Here, we studied these characteristics of NK cells in MLL-AF9 induced mouse acute myeloid leukemia (AML) model...
November 16, 2017: Molecular Immunology
https://www.readbyqxmd.com/read/29146966/revisiting-the-role-of-interleukin-8-in-chronic-lymphocytic-leukemia
#3
Denise Risnik, Enrique Podaza, María B Almejún, Ana Colado, Esteban E Elías, Raimundo F Bezares, Horacio Fernández-Grecco, Santiago Cranco, Julio C Sánchez-Ávalos, Mercedes Borge, Romina Gamberale, Mirta Giordano
The proliferation and survival of malignant B cells in chronic lymphocytic leukemia (CLL) depend on signals from the microenvironment in lymphoid tissues. Among a plethora of soluble factors, IL-8 has been considered one of the most relevant to support CLL B cell progression in an autocrine fashion, even though the expression of IL-8 receptors, CXCR1 and CXCR2, on leukemic B cells has not been reported. Here we show that circulating CLL B cells neither express CXCR1 or CXCR2 nor they respond to exogenous IL-8 when cultured in vitro alone or in the presence of monocytes/nurse-like cells...
November 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29137597/reduction-of-pluripotent-gene-expression-in-murine-embryonic-stem-cells-exposed-to-mechanical-loading-or-cyclo-rgd-peptide
#4
Olesja Hazenbiller, Neil A Duncan, Roman J Krawetz
BACKGROUND: Self-renewal and differentiation of embryonic stem cells (ESCs) is directed by biological and/or physical cues that regulate multiple signaling cascades. We have previously shown that mESCs seeded in a type I collagen matrix demonstrate a loss of pluripotent marker expression and differentiate towards an osteogenic lineage. In this study, we examined if this effect was mediated in part through Arginylglycylaspartic acid (RGD) dependent integrin activity and/or mechano-transduction...
November 14, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/29137349/tumor-trp53-status-and-genotype-affect-the-bone-marrow-microenvironment-in-acute-myeloid-leukemia
#5
Rodrigo Jacamo, R Eric Davis, Xiaoyang Ling, Sonali Sonnylal, Zhiqiang Wang, Wencai Ma, Min Zhang, Peter Ruvolo, Vivian Ruvolo, Rui-Yu Wang, Teresa McQueen, Scott Lowe, Johannes Zuber, Steven M Kornblau, Marina Konopleva, Michael Andreeff
The genetic heterogeneity of acute myeloid leukemia (AML) and the variable responses of individual patients to therapy suggest that different AML genotypes may influence the bone marrow (BM) microenvironment in different ways. We performed gene expression profiling of bone marrow mesenchymal stromal cells (BM-MSC) isolated from normal C57BL/6 mice or mice inoculated with syngeneic murine leukemia cells carrying different human AML genotypes, developed in mice with Trp53 wild-type or nullgenetic backgrounds...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137304/monocarboxylate-transporter-1-mct1-a-tool-to-stratify-acute-myeloid-leukemia-aml-patients-and-a-vehicle-to-kill-cancer-cells
#6
Filipa Lopes-Coelho, Carolina Nunes, Sofia Gouveia-Fernandes, Rita Rosas, Fernanda Silva, Paula Gameiro, Tânia Carvalho, Maria Gomes da Silva, José Cabeçadas, Sérgio Dias, Luís G Gonçalves, Jacinta Serpa
Dysregulation of glucose/lactate dynamics plays a role in cancer progression, and MCTs are key elements in metabolic remodeling. VEGF is a relevant growth factor in the maintenance of bone marrow microenvironment and it is also important in hematological diseases. Our aim was to investigate the role of VEGF in the metabolic adaptation of Acute myeloid leukemia (AML) cells by evaluating the metabolic profiles and cell features according to the AML lineage and testing lactate as a metabolic coin. Our in vitro results showed that AML promyelocytic (HL60) and monocytic (THP1) (but not erythroid- HEL) lineages are well adapted to VEGF and lactate rich environment...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29122993/the-microenvironmental-stromal-cells-abrogate-nf-%C3%AE%C2%BAb-inhibitor-induced-apoptosis-in-chronic-lymphocytic-leukemia
#7
Carl Philipp Simon-Gabriel, Katharina Foerster, Shifa Saleem, Dorothee Bleckmann, Marco Benkisser-Petersen, Nicolas Thornton, Kazuo Umezawa, Sarah Decker, Meike Burger, Hendrik Veelken, Rainer Claus, Christine Dierks, Justus Duyster, Katja Zirlik
NF-κB is known to play an important role in the pathogenesis of chronic lymphocytic leukemia. Several NF-κB inhibitors have been shown to successfully induce apoptosis of chronic lymphocytic leukemia cells in vitro. Since the microenvironment is known to be crucial for the survival of chronic lymphocytic leukemia cells, we tested here whether NF-κB inhibition may still induce apoptosis in these leukemic cells in the presence of protective stromal interaction. We used the specific NF-κB inhibitor Dehydroxymethylepoxyquinomicin...
November 9, 2017: Haematologica
https://www.readbyqxmd.com/read/29117945/adipocytes-sequester-and-metabolize-the-chemotherapeutic-daunorubicin
#8
Xia Sheng, Jean-Hugues Parmentier, Jonathan Tucci, Hua Pei, Omar Cortez-Toledo, Christina M Dieli-Conwright, Matthew J Oberley, Michael Neely, Etan Orgel, Stan G Louie, Steven D Mittelman
Obesity is associated with poorer outcome for many cancers. Previously, we observed that adipocytes protect acute lymphoblastic leukemia (ALL) cells from the anthracycline, daunorubicin. In this study, it is determined whether adipocytes clear daunorubicin from the tumor microenvironment (TME). Intracellular daunorubicin concentrations were evaluated using fluorescence. Daunorubicin and its largely inactive metabolite, daunorubicinol, were analytically measured in media, cells, and tissues using liquid chromatography/mass spectrometry (LC/MS)...
November 8, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29102598/dicer1-gene-and-mirna-dysregulation-in-mesenchymal-stem-cells-of-patients-with-myelodysplastic-syndrome-and-acute-myeloblastic-leukemia
#9
Hakan Ozdogan, Bala Gur Dedeoglu, Yasemin Oztemur Islakoglu, Alp Aydos, Sevil Kose, Arzu Atalay, Zeynep Arzu Yegin, Ferit Avcu, Duygu Uckan Cetinkaya, Osman Ilhan
Multipotent mesenchymal stem cells (MSC) are key components of the bone marrow (BM) microenvironment. The contribution of this microenvironment to the pathophysiology of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is not well defined. A recent study in mice demonstrated that DICER1 gene deletion in osteoprogenitor cells from the BM microenvironment suppressed osteogenic differentiation and induced MDS and AML-like haematological findings. The present study evaluated the expression profiles of microRNAs (miRNAs) and DICER1 gene in BM-derived MSC of patients with AML (n=12), MDS (n=10) and healthy controls (HC) (n=8)...
October 31, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29096333/distinct-ephb4-mediated-mechanisms-of-apoptotic-and-resistance-to-dasatinib-in-human-chronic-myeloid-leukemia-and-k562-cell-lines
#10
Wei-Hong Zhao, Bin-Tao Huang, Jian-Yu Zhang, Qing-Chun Zeng
OBJECTIVE: To determine the role and mechanism of EphB4 in dasatinib (DAS) resistance in advanced chronic myeloid leukemia (CML), we explored the EphB4-mediated apoptotic and matrix microenvironment pathway in human CML and K562 cell lines. METHOD: Heparinized bone marrow samples were obtained from enrolled five patients (identified as A to E and visits identified by number) at initial diagnosis (A1-E1) and in the DAS-resistance advanced phase (A2-E2). Meanwhile, highly DAS-resistant cells, named K562-R cells, were obtained from K562-W cells with increasing concentrations of DAS...
October 27, 2017: Leukemia Research
https://www.readbyqxmd.com/read/29079582/c-mpl-provides-tumor-targeted-t-cell-receptor-transgenic-t-cells-with-co-stimulation-and-cytokine-signals
#11
Christopher D Nishimura, Daniel A Brenner, Malini Mukherjee, Rachel A Hirsch, Leah Ott, Meng-Fen Wu, Hao Liu, Olga Dakhova, Jordan S Orange, Malcolm K Brenner, Charles Y Lin, Caroline Arber
Adoptively transferred T cell receptor (TCR)-engineered T-cells depend on host-derived co-stimulation and cytokine signals for their full and sustained activation. However, in cancer patients both signals are frequently impaired. Hence, we developed a novel strategy that combines both essential signals in one transgene by expressing the non-lymphoid hematopoietic growth factor receptor c-MPL (myeloproliferative leukemia), the receptor for thrombopoietin (TPO), in T-cells. C-MPL signaling activates pathways shared with conventional co-stimulatory and cytokine receptor signaling...
October 27, 2017: Blood
https://www.readbyqxmd.com/read/29070098/-distribution-of-type-9-t-helper-cells-and-expression-of-transcriptional-factors-in-acute-myeloid-leukemia
#12
Hui Yang, Hai-Rong Qiu, Rong Wang, Rui Guo, Yan Wang, Hui Wang, Yu-Jie Wu, Jian-Fu Zhang, Lei Fan, Si-Xuan Qian, Wei Xu, Jian-Yong Li
OBJECTIVE: To investigate the distribution of T helper (Th9) cells and its relationship with clinical characteristics of patients with acute myeloid leukemia (AML), and to analyze the activating levels of different transcriptional factors in Th9 cells. METHODS: The peripheral blood specimens of 102 AML patients and 83 healthy persons as controls were collected, then the T cells of peripheral blood in AML patients and controls were isolated by using CD3 magnetic beads, the mRNA expression of IL-9 was detected by real-time quantitative PCR, the Th9(CD4(+)IL-9(+)) cell levels in diffrent stages and activating level of Th9 coexpression with IL-9 were detected by flow cytometry...
October 2017: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/29069828/neutrophils-protect-lymphoma-cells-against-cytotoxic-and-targeted-therapies-through-cd11b-icam-1-binding
#13
Taghreed Hirz, Eva-Laure Matera, Kamel Chettab, Lars Petter Jordheim, Doriane Mathé, Anne Evesque, Justine Esmenjaud, Gilles Salles, Charles Dumontet
Innate immune cells constitute a substantial proportion of the cells within the tumor microenvironment. Besides the contribution of the microenvironment to tumor proliferation and survival, there is direct evidence that interactions between tumor cells and their microenvironment alter sensitivity to anti-cancer agents. Neutrophils, a key player in the innate immune system, have been less studied than many other immune cells regarding their impact on cancer cell response to anti-cancer agents. In our 2D and 3D coculture systems, human neutrophils and differentiated HL60 cells attenuated the sensitivity of various lymphoma cell lines to several anti-cancer agents, including targeted therapies...
September 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29064484/jam-a-as-a-prognostic-factor-and-new-therapeutic-target-in-multiple-myeloma
#14
A G Solimando, A Brandl, K Mattenheimer, C Graf, M Ritz, A Ruckdeschel, T Stühmer, Z Mokhtari, M Rudelius, J Dotterweich, M Bittrich, V Desantis, R Ebert, P Trerotoli, M A Frassanito, A Rosenwald, A Vacca, H Einsele, F Jakob, A Beilhack
Cell adhesion in the multiple myeloma (MM) microenvironment has been recognized as a major mechanism of MM cell survival and the development of drug resistance. Here we addressed the hypothesis that the protein junctional adhesion molecule-A (JAM-A) may represent a novel target and a clinical biomarker in MM. We evaluated JAM-A expression in MM cell lines and in 147 MM patient bone marrow aspirates and biopsies at different disease stages. Elevated JAM-A levels in patient-derived plasma cells were correlated with poor prognosis...
September 28, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29054417/the-regulation-of-pathways-of-inflammation-and-resolution-in-immune-cells-and-cancer-stem-cells-by-selenium
#15
Bastihalli T Diwakar, Arvind M Korwar, Robert F Paulson, K Sandeep Prabhu
Cancer is a complex disease where cancer stem cells (CSCs) maintain unlimited replicative potential, but evade chemotherapy drugs through cellular quiescence. CSCs are able to give rise to bulk tumor cells that have the capability to override antiproliferative signals and evade apoptosis. Numerous pathways are dysregulated in tumor cells, where increased levels of prooxidant reactive oxygen and nitrogen species can lead to localized inflammation to exacerbate all three stages of tumorigenesis: initiation, progression, and metastasis...
2017: Advances in Cancer Research
https://www.readbyqxmd.com/read/29048660/canonical-and-non-canonical-wnt-signaling-in-cancer-stem-cells-and-their-niches-cellular-heterogeneity-omics-reprogramming-targeted-therapy-and-tumor-plasticity-review
#16
Masaru Katoh
Cancer stem cells (CSCs), which have the potential for self-renewal, differentiation and de-differentiation, undergo epigenetic, epithelial-mesenchymal, immunological and metabolic reprogramming to adapt to the tumor microenvironment and survive host defense or therapeutic insults. Intra-tumor heterogeneity and cancer-cell plasticity give rise to therapeutic resistance and recurrence through clonal replacement and reactivation of dormant CSCs, respectively. WNT signaling cascades cross-talk with the FGF, Notch, Hedgehog and TGFβ/BMP signaling cascades and regulate expression of functional CSC markers, such as CD44, CD133 (PROM1), EPCAM and LGR5 (GPR49)...
September 19, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29030004/hepatic-leukemia-associated-macrophages-exhibit-a-pro-inflammatory-phenotype-in-notch1-induced-acute-t-cell-leukemia
#17
Xiao Yang, Wenli Feng, Rong Wang, Feifei Yang, Lina Wang, Shayan Chen, Chong Chen, Qian Ren, Guoguang Zheng
Tumor-associated macrophages (TAMs) are well accepted and the pathological role of macrophages in hematopoietic malignancies have been proposed. Hepatomegaly is frequently observed in T cell acute lymphoblastic leukemia (T-ALL) patients with poor prognosis. However, the role of leukemia-associated macrophages (LAMs) in hepatic microenvironment remains unclear. Here, the characteristics of hepatic LAMs (H-LAMs) were studied in Notch1 induced T-ALL model. Increase in proportion and absolute counts of H-LAMs was detected with infiltration of inflammatory cells...
October 4, 2017: Immunobiology
https://www.readbyqxmd.com/read/29023488/transgenic-expression-of-human-cytokines-in-immunodeficient-mice-does-not-facilitate-myeloid-expansion-of-bcr-abl1-transduced-human-cord-blood-cells
#18
Maria Askmyr, Sofia von Palffy, Nils Hansen, Niklas Landberg, Carl Högberg, Marianne Rissler, Helena Ågerstam, Thoas Fioretos
Several attempts have been made to model chronic myeloid leukemia (CML) in a xenograft setting but expansion of human myeloid cells in immunodeficient mice has proven difficult to achieve. Lack of cross-reacting cytokines in the microenvironment of the mice has been proposed as a potential reason. In this study we have used NOD/SCID IL2-receptor gamma deficient mice expressing human SCF, IL-3 and GM-CSF (NSGS mice), that should be superior in supporting human, and particularly, myeloid cell engraftment, to expand BCR-ABL1 expressing human cells in order to model CML...
2017: PloS One
https://www.readbyqxmd.com/read/29018147/acute-lymphoblastic-leukemia-relapse-after-cd19-targeted-chimeric-antigen-receptor-t-cell-therapy
#19
REVIEW
Jiasheng Wang, Yongxian Hu, He Huang
CART19 therapy has revolutionized the treatment of CD19(+) acute lymphoblastic leukemia, demonstrating an unprecedented complete remission rate; however, as follow-up prolongs, a high relapse rate after CART19 therapy has emerged as one of the major problems. Relapse can be attributed to the loss of leukemic cell immunogenicity, diminished function and amount of CART19 cells, and the inhibitory bone marrow microenvironment. Although studies to prevent and treat relapse have begun, some encouraging results have demonstrated the possibility of decreasing the relapse rate...
October 10, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28978838/chronic-lymphocytic-leukemia-biology-disease-progression-and-current-treatment-strategies
#20
Takahiro Yano
Chronic lymphocytic leukemia (CLL) is characterized by clonal proliferation and accumulation of mature CD5-positive, CD10-negative, CD20 weakly positive, and CD23-positive B-cells within blood, bone marrow, lymph nodes, and spleen. In proliferation centers, the survival and growth of CLL cells requires a permissive microenvironment comprising T-cells, macrophages, and stromal cells. FISH analysis has revealed that almost 80% of CLL cases carry chromosomal abnormalities including the most frequent del (13q14) and the strongest poor prognostic factor del (17p), both related to TP53 mutations...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
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