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https://www.readbyqxmd.com/read/29846239/exosomes-in-acute-myeloid-leukemia-inhibit-hematopoiesis
#1
Michael Boyiadzis, Theresa L Whiteside
PURPOSE OF REVIEW: Exosomes are cell-derived, biologically active membrane-bound vesicles, and are emerging as key modulators of hematopoiesis. Recent studies have provided a clearer understanding of the mechanisms whereby blast-derived exosomes act to suppress hematopoiesis in acute myeloid leukemia (AML). RECENT FINDINGS: Exosomes released from leukemia blasts have been shown to suppress hematopoietic progenitor cell (HPC) functions indirectly through stromal reprogramming of niche-retention factors and also as a consequence of AML exosome-directed microRNA delivery to HPC...
May 24, 2018: Current Opinion in Hematology
https://www.readbyqxmd.com/read/29802118/dis3-isoforms-vary-in-their-endoribonuclease-activity-and-are-differentially-expressed-within-haematological-cancers
#2
Sophie R Robinson, Sandra C Viegas, Rute G Matos, Susana Domingues, Marisa Bedir, Helen J S Stewart, Timothy J Chevassut, Antony W Oliver, Cecilia M Arraiano, Sarah F Newbury
DIS3 is the catalytic subunit of the exosome, a protein complex involved in the 3' to 5' degradation of RNAs. DIS3 is a highly conserved exoribonuclease, also known as Rrp44. Global sequencing studies have identified DIS3 as being mutated in a range of cancers, with a considerable incidence in multiple myeloma. In this work, we have identified two protein-coding isoforms of DIS3. Both isoforms are functionally relevant and result from alternative splicing. They differ from each other in the size of their N-terminal PIN domain, which has been shown to have endoribonuclease activity and tether DIS3 to the exosome...
May 25, 2018: Biochemical Journal
https://www.readbyqxmd.com/read/29752284/analysis-of-the-thrombotic-and-fibrinolytic-activities-of-tumor-cell-derived-extracellular-vesicles
#3
Ludovic Durrieu, Alamelu Bharadwaj, David M Waisman
Exosomes and microvesicles (MVs) are small extracellular vesicles secreted by tumor cells and are suggested to contribute to the thrombotic events that commonly occur in patients with advanced malignancies. Paradoxically, these vesicles have been reported to also possess fibrinolytic activity. To determine whether thrombotic or fibrinolytic activity is a predominant characteristic of these extracellular vesicles, we prepared exosomes and MVs from 2 breast cancer cell lines (MDA-MB-231 and MCF7), a lung cancer cell line (A549), and a leukemia cell line (NB4) and assayed their thrombotic and fibrinolytic activities...
May 22, 2018: Blood Advances
https://www.readbyqxmd.com/read/29740437/targeting-and-therapy-of-glioblastoma-in-a-mouse-model-using-exosomes-derived-from-natural-killer-cells
#4
Liya Zhu, Ji Min Oh, Prakash Gangadaran, Senthilkumar Kalimuthu, Se Hwan Baek, Shin Young Jeong, Sang-Woo Lee, Jaetae Lee, Byeong-Cheol Ahn
Objective: Glioblastoma is a highly aggressive primary brain tumor that is resistant to radiotherapy and chemotherapy. Natural killer (NK) cells have been used to treat incurable cancers. Recent studies have investigated the effectiveness of NK-cell-derived exosomes (NK-Exo) for treating incurable cancers such as melanoma, leukemia, and neuroblastoma; however, NK-Exo have not been used to treat glioblastoma. In the present study, we investigated the antitumor effects of NK-Exo against aggressive glioblastoma both in vitro and in vivo and determined the tumor-targeting ability of NK-Exo by performing fluorescence imaging...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29499908/cd21-independent-epstein-barr-virus-entry-into-nk-cells
#5
Jeong Hoo Lee, Jahyang Choi, Yong-Oon Ahn, Tae Min Kim, Dae Seog Heo
Extranodal natural killer (NK)/T-cell lymphoma is an aggressive malignant disease that is associated with Epstein-Barr viral (EBV) infection. To date, the mechanism of viral entry into NK cells remains uncertain. Here, we investigated this mechanism using human NK cells in vitro. CD21 mRNA expression, an EBV-entry receptor, was transiently detected in NK cells after exosome treatment, and levels decreased after further culture. CD21 protein expression was also transiently transferred to NK cells after co-culture with an EBV-positive Burkitt lymphoma cell line (Raji) via trogocytosis...
May 2018: Cellular Immunology
https://www.readbyqxmd.com/read/29479064/mir-34c-5p-promotes-eradication-of-acute-myeloid-leukemia-stem-cells-by-inducing-senescence-through-selective-rab27b-targeting-to-inhibit-exosome-shedding
#6
Danyue Peng, Huifang Wang, Lei Li, Xiao Ma, Ying Chen, Hao Zhou, Yi Luo, Yin Xiao, Lingbo Liu
Leukemia stem cells (LSCs) are responsible for acute myeloid leukemia (AML) chemotherapy resistance and relapse. Here, we discovered that miR-34c-5p, a microRNA central to the senescence regulation network, was significantly down-regulated in AML (non-acute promyelocytic leukemia, non-APL) stem cells compared to that in normal hematopoietic stem cells (HSCs). The lower expression of miR-34c-5p in LSCs was closely correlated to the adverse prognosis and poor responses to therapy of AML patients. Increased miR-34c-5p expression induced LSCs senescence ex vivo, prevented leukemia development and promoted the eradication of LSCs in immune deficient mice...
May 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/29345286/cyclooxygenase-2-expression-is-induced-by-celecoxib-treatment-in-lung-cancer-cells-and-is-transferred-to-neighbor-cells-via-exosomes
#7
Jayoung Kim, Seung-Woo Hong, Seonghan Kim, Daejin Kim, Dae Young Hur, Dong-Hoon Jin, Bomi Kim, Yeong Seok Kim
Lung cancer is one of most common types of cancer worldwide. Lung cancer results in a death higher rate each year compared to colon, breast and prostate cancer combined. Celecoxib is a selective inhibitor of cyclooxygenase-2 (COX‑2), an enzyme of which the expression is induced by various stimuli, such as inflammation. In addition, celecoxib triggers COX-2 loading on exosomes. Exosomes are small vesicles composed of a lipid bilayer membrane and are found in most biological fluids, such as blood breast milk and urine...
February 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29223442/exosomes-derived-from-imatinib-resistant-chronic-myeloid-leukemia-cells-mediate-a-horizontal-transfer-of-drug-resistant-trait-by-delivering-mir-365
#8
Qing-Hua Min, Xiao-Zhong Wang, Jing Zhang, Qing-Gen Chen, Shu-Qi Li, Xiao-Qing Liu, Jing Li, Jing Liu, Wei-Ming Yang, Yu-Huan Jiang, Yan-Mei Xu, Jin Lin, Qiu-Fang Gao, Fan Sun, Lei Zhang, Bo Huang
Chronic myeloid leukemia (CML) is a malignant disorder of hematopoietic stem/progenitor cells. Majority of patients can be effectively treated with tyrosine kinase inhibitors (TKIs) such as imatinib, but a portion of patients will develop drug resistance. Accumulated evidences have identified exosomes in cancer as promoters of tumor progression. Herein, we found that exosomes derived from imatinib resistant CML cells can be internalized into sensitive CML cells and confer drug-resistance traits. We also demonstrated a significant higher level of miR-365 in exosomes derived from drug-resistant CML cells compared with those from sensitive ones using microarray and qRT-PCR...
January 15, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29130994/enhancement-of-anti-leukemia-immunity-by-leukemia-derived-exosomes-via-downregulation-of-tgf-%C3%AE-1-expression
#9
Fang Huang, Jiangbo Wan, Weiwei Hu, Siguo Hao
BACKGROUND/AIMS: Minimal residual leukemia cells (MRLs) are difficult to eradicate through traditional treatment and therefore remain to be a major threat to the long-term survival of leukemia patients. Tumor-derived exosomes (TEXs), which carry tumor associated antigens (TAA), may be a potential cell-free tumor vaccine for the specific eradication of MRLs. However, TEXs are intended to be less immunogenic due to exosomal TGF-β1. To further optimize the efficacy of TEX-based vaccines, we investigated whether exosomes from TGF-β1 silenced leukemia cells (LEXTGF-β1si) had an increased potential to induce a specific antitumor effect compared with non-modified exosomes...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29099772/role-of-lfa-1-and-icam-1-in-cancer
#10
REVIEW
Manuel Reina, Enric Espel
The lymphocyte function-associated antigen-1 (LFA-1) (also known as CD11a/CD18 and αL β₂), is just one of many integrins in the human body, but its significance is derived from its exclusive presence in leukocytes. In this review, we summarize the studies relating LFA-1 and its major ligand ICAM-1 (or CD54) with cancer, through the function of lymphocytes and myeloid cells on tumor cells. We consider how LFA-1 mediates the interaction of leukocytes with tumors and the role of ICAM-1 in tumor dynamics, which can be independent of its interaction with LFA-1...
November 3, 2017: Cancers
https://www.readbyqxmd.com/read/29089618/circulating-exosomes-carrying-an-immunosuppressive-cargo-interfere-with-cellular-immunotherapy-in-acute-myeloid-leukemia
#11
Chang-Sook Hong, Priyanka Sharma, Saigopalakrishna S Yerneni, Patricia Simms, Edwin K Jackson, Theresa L Whiteside, Michael Boyiadzis
Exosomes, small (30-150 nm) extracellular vesicles (EVs) isolated from plasma of patients with acute myeloid leukemia (AML) carry leukemia-associated antigens and multiple inhibitory molecules. Circulating exosomes can deliver suppressive cargos to immune recipient cells, inhibiting anti-tumor activities. Pre-therapy plasma of refractory/relapsed AML patients contains elevated levels of immunosuppressive exosomes which interfere with anti-leukemia functions of activated immune cells. We show that exosomes isolated from pre-therapy plasma of the AML patients receiving adoptive NK-92 cell therapy block anti-leukemia cytotoxicity of NK-92 cells and other NK-92 cell functions...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29080983/autoimmune-responses-to-exosomes-and-candidate-antigens-contribute-to-type-1-diabetes-in-non-obese-diabetic-mice
#12
REVIEW
Yang D Dai, Huiming Sheng, Peter Dias, M Jubayer Rahman, Roman Bashratyan, Danielle Regn, Kristi Marquardt
PURPOSE OF REVIEW: The initial autoimmune trigger of type 1 diabetes (T1D) remains unclear. In non-obese diabetic (NOD) mice, islet inflammation starts early in life, suggesting the presence of an endogenous trigger for the spontaneous autoimmune response in this T1D mouse model. In this review, we argue that abnormal release of exosomes might be the trigger of the early inflammatory and autoimmune responses in the islets. RECENT FINDINGS: Exosomes are nano-sized membrane complexes that are secreted by cells following fusion of late endosomes and/or multivesicular bodies with the plasma membrane...
October 28, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28918518/micro-rna-profiling-of-exosomes-from-marrow-derived-mesenchymal-stromal-cells-in-patients-with-acute-myeloid-leukemia-implications-in-leukemogenesis
#13
Juliana Barrera-Ramirez, Jessie R Lavoie, Harinad B Maganti, William L Stanford, Caryn Ito, Mitchell Sabloff, Marjorie Brand, Michael Rosu-Myles, Yevgeniya Le, David S Allan
Gene regulatory networks in AML may be influenced by microRNAs (miRs) contained in exosomes derived from bone marrow mesenchymal stromal cells (MSCs). We sequenced miRs from exosomes isolated from marrow-derived MSCs from patients with AML (n = 3) and from healthy controls (n = 3; not age-matched). Known targets of mIRs that were significantly different in AML-derived MSC exosomes compared to controls were identified. Of the five candidate miRs identified by differential packaging in exosomes, only miR-26a-5p and miR-101-3p were significantly increased in AML-derived samples while miR-23b-5p, miR-339-3p and miR-425-5p were significantly decreased...
December 2017: Stem Cell Reviews
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...
March 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28776566/response-commentary-exosomes-vs-microvesicles-in-hematological-malignancies
#15
T L Whiteside, M Boyiadzis
No abstract text is available yet for this article.
October 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28775118/chronic-lymphocytic-leukemia-cells-are-active-participants-in-microenvironmental-cross-talk
#16
REVIEW
Martijn Ha van Attekum, Eric Eldering, Arnon P Kater
The importance of the tumor microenvironment in chronic lymphocytic leukemia is widely accepted. Nevertheless, the understanding of the complex interplay between the various types of bystander cells and chronic lymphocytic leukemia cells is incomplete. Numerous studies have indicated that bystander cells provide chronic lymphocytic leukemia-supportive functions, but it has also become clear that chronic lymphocytic leukemia cells actively engage in the formation of a supportive tumor microenvironment through several cross-talk mechanisms...
September 2017: Haematologica
https://www.readbyqxmd.com/read/28754746/tumor-derived-exosomes-modulate-pd-l1-expression-in-monocytes
#17
Franziska Haderk, Ralph Schulz, Murat Iskar, Laura Llaó Cid, Thomas Worst, Karolin V Willmund, Angela Schulz, Uwe Warnken, Jana Seiler, Axel Benner, Michelle Nessling, Thorsten Zenz, Maria Göbel, Jan Dürig, Sven Diederichs, Jérôme Paggetti, Etienne Moussay, Stephan Stilgenbauer, Marc Zapatka, Peter Lichter, Martina Seiffert
In chronic lymphocytic leukemia (CLL), monocytes and macrophages are skewed toward protumorigenic phenotypes, including the release of tumor-supportive cytokines and the expression of immunosuppressive molecules such as programmed cell death 1 ligand 1 (PD-L1). To understand the mechanism driving protumorigenic skewing in CLL, we evaluated the role of tumor cell-derived exosomes in the cross-talk with monocytes. We carried out RNA sequencing and proteome analyses of CLL-derived exosomes and identified noncoding Y RNA hY4 as a highly abundant RNA species that is enriched in exosomes from plasma of CLL patients compared with healthy donor samples...
July 28, 2017: Science Immunology
https://www.readbyqxmd.com/read/28656959/do-we-need-to-distinguish-exosomes-from-microvesicles-in-hematological-malignancies
#18
A Caivano, L Del Vecchio, P Musto
No abstract text is available yet for this article.
September 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28601924/tgf-%C3%AE-1-silenced-leukemia-cell-derived-exosomes-target-dendritic-cells-to-induce-potent-anti-leukemic-immunity-in-a-mouse-model
#19
Fang Huang, Jiangbo Wan, Siguo Hao, Xiaohui Deng, Linjun Chen, Liyuan Ma
Tumor-derived exosomes (TEX) can induce a specific antitumor immune response and have been developed as a promising tumor vaccine. Despite promising preclinical data, TEX exhibit relatively low efficacy and limited clinical benefit in clinical trials. In the present study, we investigated whether exosomes from the TGF-β1 silenced L1210 cells (LEXTGF-β1si ) can enhance the efficacy of DC-based vaccines. We silenced TGF-β1 in L1210 cells with a lentiviral shRNA vector and prepared the LEXTGF-β1si . It was shown that LEXTGF-β1si can significantly decrease TGF-β1 expression of dendritic cells (DC) and effectively promote their maturation and immune function...
October 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28596424/s100-a9-protein-in-exosomes-from-chronic-lymphocytic-leukemia-cells-promotes-nf-%C3%AE%C2%BAb-activity-during-disease-progression
#20
Daniel Prieto, Natalia Sotelo, Noé Seija, Sandra Sernbo, Cecilia Abreu, Rosario Durán, Magdalena Gil, Estefanía Sicco, Victoria Irigoin, Carolina Oliver, Ana Inés Landoni, Raúl Gabus, Guillermo Dighiero, Pablo Oppezzo
Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by accumulation of clonal B lymphocytes, resulting from a complex balance between cell proliferation and apoptotic death. Continuous crosstalk between cancer cells and local/distant host environment is required for effective tumor growth. Among the main actors of this dynamic interplay between tumoral cells and their microenvironment are the nano-sized vesicles called exosomes. Emerging evidence indicates that secretion, composition, and functional capacity of exosomes are altered as tumors progress to an aggressive phenotype...
August 10, 2017: Blood
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