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https://www.readbyqxmd.com/read/27835864/senescent-stromal-cell-induced-divergence-and-therapeutic-resistance-in-t-cell-acute-lymphoblastic-leukemia-lymphoma
#1
David M Habiel, Nicolas Krepostman, Michael Lilly, Karen Cavassani, Ana Lucia Coelho, Takehiko Shibata, Kojo Elenitoba-Johnson, Cory M Hogaboam
T cell Acute Lymphoblastic Leukemia/Lymphoma (T-ALL/LBL) is a precursor T cell leukemia/lymphoma that represents approximately 15% of all childhood and 25% of adult acute lymphoblastic leukemia. Although a high cure rate is observed in children, therapy resistance is often observed in adults and mechanisms leading to this resistance remain elusive. Utilizing public gene expression datasets, a fibrotic signature was detected in T-LBL but not T-ALL biopsies. Further, using a T-ALL cell line, CCRF-CEM (CEM) cells, we show that CEM cells induce pulmonary remodeling in immunocompromised mice, suggesting potential interaction between these cells and lung fibroblasts...
November 7, 2016: Oncotarget
https://www.readbyqxmd.com/read/27797340/sorting-protein-vps33b-regulates-exosomal-autocrine-signaling-to-mediate-hematopoiesis-and-leukemogenesis
#2
Hao Gu, Chiqi Chen, Xiaoxin Hao, Conghui Wang, Xiaocui Zhang, Zhen Li, Hongfang Shao, Hongxiang Zeng, Zhuo Yu, Li Xie, Fangzhen Xia, Feifei Zhang, Xiaoye Liu, Yaping Zhang, Haishan Jiang, Jun Zhu, Jiangbo Wan, Chun Wang, Wei Weng, Jingjing Xie, Minfang Tao, Cheng Cheng Zhang, Junling Liu, Guo-Qiang Chen, Junke Zheng
Certain secretory proteins are known to be critical for maintaining the stemness of stem cells through autocrine signaling. However, the processes underlying the biogenesis, maturation, and secretion of these proteins remain largely unknown. Here we demonstrate that many secretory proteins produced by hematopoietic stem cells (HSCs) undergo exosomal maturation and release that is controlled by vacuolar protein sorting protein 33b (VPS33B). Deletion of VPS33B in either mouse or human HSCs resulted in impaired exosome maturation and secretion as well as loss of stemness...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27760548/atl-derived-exosomes-modulate-mesenchymal-stem-cells-potential-role-in-leukemia-progression
#3
Jamal El-Saghir, Farah Nassar, Nadim Tawil, Marwan El-Sabban
BACKGROUND: Exosomes are membrane nano-vesicles secreted by a multitude of cells that harbor biological constituents such as proteins, lipids, mRNA and microRNA. Exosomes can potentially transfer their cargo to other cells, implicating them in many patho-physiological processes. Mesenchymal stem cells (MSCs), residents of the bone marrow and metastatic niches, potentially interact with cancer cells and/or their derived exosomes. In this study, we investigated whether exosomes derived from adult T-cell leukemia/lymphoma (ATL) cells act as intercellular messengers delivering leukemia-related genes that modulate the properties of human MSCs in favor of leukemia...
October 19, 2016: Retrovirology
https://www.readbyqxmd.com/read/27725845/exosome-mediated-growth-effect-on-the-non-growing-pre-b-acute-lymphoblastic-leukemia-cells-at-low-starting-cell-density
#4
Sapan J Patel, Costel C Darie, Bayard D Clarkson
Tumors contain heterogeneous cell populations and achieve dominance by functioning as collective systems. The mechanisms underlying the aberrant growth and interactions between cells are not very well understood. The pre-B acute lymphoblastic leukemia cells we studied were obtained directly from a patient with Ph+ ALL. A new Ph+ ALL cell line (ALL3) was established from the leukemic cells growing as ascitic cells in his pleural fluid. The patient died of his disease shortly after the cells were obtained. ALL3 cells grow well at high cell densities (HD), but not at low cell densities...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27601730/aml-suppresses-hematopoiesis-by-releasing-exosomes-that-contain-micrornas-targeting-c-myb
#5
Noah I Hornick, Ben Doron, Sherif Abdelhamed, Jianya Huan, Christina A Harrington, Rongkun Shen, Xiaolu A Cambronne, Santhosh Chakkaramakkil Verghese, Peter Kurre
Exosomes are paracrine regulators of the tumor microenvironment and contain complex cargo. We previously reported that exosomes released from acute myeloid leukemia (AML) cells can suppress residual hematopoietic stem and progenitor cell (HSPC) function indirectly through stromal reprogramming of niche retention factors. We found that the systemic loss of hematopoietic function is also in part a consequence of AML exosome-directed microRNA (miRNA) trafficking to HSPCs. Exosomes isolated from cultured AML or the plasma from mice bearing AML xenografts exhibited enrichment of miR-150 and miR-155...
September 6, 2016: Science Signaling
https://www.readbyqxmd.com/read/27569460/-extracellular-vesicles-and-their-role-in-hematological-malignancies
#6
Andrea Rzepiel, Nóra Kutszegi, Judit Cs Sági, Andrea Kelemen, Krisztina Pálóczi, Ágnes F Semsei, Edit Buzás, Dániel János Erdélyi
Extracellular vesicles are produced in all organisms. The most intensively investigated categories of extracellular vesicles include apoptotic bodies, microvesicles and exosomes. Among a very wide range of areas, their role has been confirmed in intercellular communication, immune response and angiogenesis (in both physiological and pathological conditions). Their alterations suggest the potential use of them as biomarkers. In this paper the authors give an insight into the research of extracellular vesicles in general, and then focus on published findings in hematological malignancies...
August 2016: Orvosi Hetilap
https://www.readbyqxmd.com/read/27191983/the-emerging-roles-of-exosomes-in-leukemogeneis
#7
Jianbiao Zhou, Sam Wang, Kangyun Sun, Wee-Joo Chng
Communication between leukemia cells and their environment is essential for the development and progression of leukemia. Exosomes are microvesicles secreted by many types of cells that contain protein and RNA and mediate intercellular communication. The involvement of exosomes has been demonstrated in the crosstalk between leukemic cells, stromal cells and endothelial cells, consequently promoting the survival of leukemic cells, protection of leukemic cells from the cytotoxic effects of chemotherapeutic drugs, angiogenesis and cell migration...
May 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27150009/mesenchymal-stromal-cell-derived-extracellular-vesicles-rescue-radiation-damage-to-murine-marrow-hematopoietic-cells
#8
S Wen, M Dooner, Y Cheng, E Papa, M Del Tatto, M Pereira, Y Deng, L Goldberg, J Aliotta, D Chatterjee, C Stewart, A Carpanetto, F Collino, S Bruno, G Camussi, P Quesenberry
Mesenchymal stromal cells (MSCs) have been shown to reverse radiation damage to marrow stem cells. We have evaluated the capacity of MSC-derived extracellular vesicles (MSC-EVs) to mitigate radiation injury to marrow stem cells at 4 h to 7 days after irradiation. Significant restoration of marrow stem cell engraftment at 4, 24 and 168 h post irradiation by exposure to MSC-EVs was observed at 3 weeks to 9 months after transplant and further confirmed by secondary engraftment. Intravenous injection of MSC-EVs to 500cGy exposed mice led to partial recovery of peripheral blood counts and restoration of the engraftment of marrow...
November 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27092489/downregulation-of-plasma-mir-215-in-chronic-myeloid-leukemia-patients-with-successful-discontinuation-of-imatinib
#9
Kazuma Ohyashiki, Tomohiro Umezu, Seiichiro Katagiri, Chiaki Kobayashi, Kenko Azuma, Tetsuzo Tauchi, Seiichi Okabe, Yutaka Fukuoka, Junko H Ohyashiki
Approximately 40% of chronic myeloid leukemia (CML) patients who discontinue imatinib (IM) therapy maintain undetectable minimal residual disease (UMRD) for more than one year (stopping IM (STOP-IM)). To determine a possible biomarker for STOP-IM CML, we examined plasma miRNA expression in CML patients who were able to discontinue IM. We first screened candidate miRNAs in unselected STOP-IM patients, who had sustained UMRD after discontinuing IM for more than six months, in comparison with healthy volunteers, by using a TaqMan low-density array for plasma or exosomes...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27070592/distinct-dasatinib-induced-mechanisms-of-apoptotic-response-and-exosome-release-in-imatinib-resistant-human-chronic-myeloid-leukemia-cells
#10
Juan Liu, Yujing Zhang, Aichun Liu, Jinghua Wang, Lianqiao Li, Xi Chen, Xinyu Gao, Yanming Xue, Xiaomin Zhang, Yao Liu
Although dasatinib is effective in most imatinib mesylate (IMT)-resistant chronic myeloid leukemia (CML) patients, the underlying mechanism of its effectiveness in eliminating imatinib-resistant cells is only partially understood. This study investigated the effects of dasatinib on signaling mechanisms driving-resistance in imatinib-resistant CML cell line K562 (K562R(IMT)). Compared with K562 control cells, exsomal release, the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/ mammalian target of rapamycin (mTOR) signaling and autophagic activity were increased significantly in K562R(IMT) cells and mTOR-independent beclin-1/Vps34 signaling was shown to be involved in exosomal release in these cells...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27050372/curcumin-modulates-chronic-myelogenous-leukemia-exosomes-composition-and-affects-angiogenic-phenotype-via-exosomal-mir-21
#11
Simona Taverna, Simona Fontana, Francesca Monteleone, Marzia Pucci, Laura Saieva, Viviana De Caro, Valeria Giunta Cardinale, Marco Giallombardo, Emanuela Vicario, Christian Rolfo, Giacomo De Leo, Riccardo Alessandro
Tumor derived exosomes are vesicles which contain proteins and microRNAs that mediate cell-cell communication and are involved in angiogenesis and tumor progression. Curcumin derived from the plant Curcuma longa, shows anticancer effects. Exosomes released by CML cells treated with Curcumin contain a high amount of miR-21 that is shuttled into the endothelial cells in a biologically active form. The treatment of HUVECs with CML Curcu-exosomes reduced RhoB expression and negatively modulated endothelial cells motility...
May 24, 2016: Oncotarget
https://www.readbyqxmd.com/read/27043038/plasma-derived-exosomes-in-acute-myeloid-leukemia-for-detection-of-minimal-residual-disease-are-we-ready
#12
Michael Boyiadzis, Theresa L Whiteside
The recent emergence of plasma-derived exosomes as biomarkers of leukemic relapse has introduced the potential for more sensitive non-invasive monitoring of leukemia patients based on the molecular and genetic analysis of the exosome cargo. In principle, the protein, lipid, miRNA, mRNA or DNA profiles of exosomes in patients' plasma that associate with leukemic relapse can be identified. The diagnostic/prognostic value of these profiles could then be validated in prospective clinical studies. Here, we consider the potential of exosomes to fulfill the role of future biomarkers of minimal residual disease in AML...
June 2016: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/26866730/exosomes-promote-bone-marrow-angiogenesis-in-hematologic-neoplasia-the-role-of-hypoxia
#13
Junko H Ohyashiki, Tomohiro Umezu, Kazuma Ohyashiki
PURPOSE OF REVIEW: To review the data on angiogenesis related to exosomes secreted by tumor cells in hematologic neoplasia and to elucidate the role of exosomes and exosomal miRNA in the bone marrow microenvironment, especially under hypoxic conditions. RECENT FINDINGS: Cross-talk between bone marrow tumor cells and surrounding cells, including endothelial cells, is important for tumor growth in hematologic neoplasia. In addition to conventional signaling pathways, exosomes, which are small endosome-derived vesicles containing miRNAs, can help to modulate the microenvironment without directly contacting nontumorous cells...
May 2016: Current Opinion in Hematology
https://www.readbyqxmd.com/read/26801919/exosomes-secreted-by-apoptosis-resistant-acute-myeloid-leukemia-aml-blasts-harbor-regulatory-network-proteins-potentially-involved-in-antagonism-of-apoptosis
#14
Anna Wojtuszkiewicz, Gerrit J Schuurhuis, Floortje L Kessler, Sander R Piersma, Jaco C Knol, Thang V Pham, Gerrit Jansen, René J P Musters, Johan van Meerloo, Yehuda G Assaraf, Gertjan J L Kaspers, Sonja Zweegman, Jacqueline Cloos, Connie R Jimenez
Expression of apoptosis-regulating proteins (B-cell CLL/lymphoma 2 - BCL-2, Myeloid Cell Leukemia 1 - MCL-1, BCL-2 like 1 - BCL-X and BCL-2-associated X protein - BAX) in acute myeloid leukemia (AML) blasts at diagnosis is associated with disease-free survival. We previously found that the initially high apoptosis-resistance of AML cells decreased after therapy, while regaining high levels at relapse. Herein, we further explored this aspect of dynamic apoptosis regulation in AML. First, we showed that the intraindividualex vivoapoptosis-related profiles of normal lymphocytes and AML blasts within the bone marrow of AML patients were highly correlated...
April 2016: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/26509439/cll-exosomes-modulate-the-transcriptome-and-behaviour-of-recipient-stromal-cells-and-are-selectively-enriched-in-mir-202-3p
#15
Mosavar Farahani, Carlos Rubbi, Luning Liu, Joseph R Slupsky, Nagesh Kalakonda
Bi-directional communication with the microenvironment is essential for homing and survival of cancer cells with implications for disease biology and behaviour. In chronic lymphocytic leukemia (CLL), the role of the microenvironment on malignant cell behaviour is well described. However, how CLL cells engage and recruit nurturing cells is poorly characterised. Here we demonstrate that CLL cells secrete exosomes that are nanovesicles originating from the fusion of multivesicular bodies with the plasma membrane, to shuttle proteins, lipids, microRNAs (miR) and mRNAs to recipient cells...
2015: PloS One
https://www.readbyqxmd.com/read/26384870/exosome-mediated-microenvironment-dysregulation-in-leukemia
#16
REVIEW
Bijender Kumar, Mayra Garcia, Jodi L Murakami, Ching-Cheng Chen
The hematopoietic stem cell (HSC) niche is composed of a complex set of stromal support cells that maintain HSCs and promote normal hematopoiesis. We now know that molecular changes within the hematopoietic niche contribute to leukemia development. Leukemia cells often reorganize the hematopoietic niche to promote and support their own survival and growth. Here we will summarize recent works that decipher the normal hematopoietic niche cellular components and describe how the leukemia-transformed niche contributes to hematological malignances...
March 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/26334291/advances-in-understanding-the-acute-lymphoblastic-leukemia-bone-marrow-microenvironment-from-biology-to-therapeutic-targeting
#17
REVIEW
Francesca Chiarini, Annalisa Lonetti, Camilla Evangelisti, Francesca Buontempo, Ester Orsini, Cecilia Evangelisti, Alessandra Cappellini, Luca M Neri, James A McCubrey, Alberto M Martelli
The bone marrow (BM) microenvironment regulates the properties of healthy hematopoietic stem cells (HSCs) localized in specific niches. Two distinct microenvironmental niches have been identified in the BM, the "osteoblastic (endosteal)" and "vascular" niches. Nevertheless, these niches provide sanctuaries where subsets of leukemic cells escape chemotherapy-induced death and acquire a drug-resistant phenotype. Moreover, it is emerging that leukemia cells are able to remodel the BM niches into malignant niches which better support neoplastic cell survival and proliferation...
March 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/26316614/exosomes-and-cafs-partners-in-crime
#18
COMMENT
Benedetta Apollonio, Alan G Ramsay
In this issue of Blood, Paggetti et al present novel findings that chronic lymphocytic leukemia (CLL)-derived exosomes and their molecular cargo are actively transferred to stromal cells that reside in the lymphoid tumor microenvironment (TME), promoting the reprogramming of these cells into cancer-associated fibroblasts (CAFs).
August 27, 2015: Blood
https://www.readbyqxmd.com/read/26305418/a-compendium-of-dis3-mutations-and-associated-transcriptional-signatures-in-plasma-cell-dyscrasias
#19
Marta Lionetti, Marzia Barbieri, Katia Todoerti, Luca Agnelli, Sonia Fabris, Giovanni Tonon, Simona Segalla, Ingrid Cifola, Eva Pinatel, Pierfrancesco Tassone, Pellegrino Musto, Luca Baldini, Antonino Neri
DIS3 is a catalytic subunit of the human exosome complex, containing exonucleolytic (RNB) and endonucleolytic (PIN) domains, recently found mutated in multiple myeloma (MM), a clinically and genetically heterogeneous form of plasma cell (PC) dyscrasia. We analyzed by next-generation sequencing (NGS) the DIS3 PIN and RNB domains in purified bone marrow PCs from 164 representative patients, including 130 cases with MM, 24 with primary PC leukemia and 10 with secondary PC leukemia. DIS3 mutations were found respectively in 18...
September 22, 2015: Oncotarget
https://www.readbyqxmd.com/read/26156801/high-serum-levels-of-extracellular-vesicles-expressing-malignancy-related-markers-are-released-in-patients-with-various-types-of-hematological-neoplastic-disorders
#20
Antonella Caivano, Ilaria Laurenzana, Luciana De Luca, Francesco La Rocca, Vittorio Simeon, Stefania Trino, Fiorella D'Auria, Antonio Traficante, Maddalena Maietti, Tiziana Izzo, Giovanni D'Arena, Giovanna Mansueto, Giuseppe Pietrantuono, Luca Laurenti, Pellegrino Musto, Luigi Del Vecchio
Many cell types release extracellular vesicles (EVs), including exosomes, microvesicles (MVs), and apoptotic bodies, which play a role in physiology and diseases. Presence and phenotype of circulating EVs in hematological malignancies (HMs) remain largely unexplored.The aim of this study was to characterize EVs in peripheral blood of HM patients compared to healthy subjects (controls). We isolated serum EVs from patients with chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL), Waldenstrom's macroglobulinemia (WM), Hodgkin's lymphoma (HL), multiple myeloma (MM), acute myeloid leukemia (AML), myeloproliferative neoplasms (MPNs), myelodysplastic syndromes (MDS), and controls...
December 2015: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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