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Autophagy leukemia

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https://www.readbyqxmd.com/read/27911437/the-role-of-the-proteasome-in-aml
#1
REVIEW
C M Csizmar, D-H Kim, Z Sachs
Acute myeloid leukemia (AML) is deadly hematologic malignancy. Despite a well-characterized genetic and molecular landscape, targeted therapies for AML have failed to significantly improve clinical outcomes. Over the past decade, proteasome inhibition has been demonstrated to be an effective therapeutic strategy in several hematologic malignancies. Proteasome inhibitors, such as bortezomib and carfilzomib, have become mainstays of treatment for multiple myeloma and mantle cell lymphoma. In light of this success, there has been a surge of literature exploring both the role of the proteasome and the effects of proteasome inhibition in AML...
December 2, 2016: Blood Cancer Journal
https://www.readbyqxmd.com/read/27902471/autophagy-autophagy-associated-adaptive-immune-responses-and-its-role-in-hematologic-malignancies
#2
REVIEW
Liangshun You, Shenhe Jin, Li Zhu, Wenbin Qian
Autophagy is a tightly regulated catabolic process that leads to the degradation of cytoplasmatic components such as aggregated/misfolded proteins and organelles through the lysosomal machinery. Recent studies suggest that autophagy plays such a role in the context of the anti-tumor immune response, make it an attractive target for cancer immunotherapy. Defective autophagy in hematopoietic stem cells may contribute to the development of hematologic malignancies, including leukemia, myelodysplastic syndrome, and lymphoproliferative disorder...
November 25, 2016: Oncotarget
https://www.readbyqxmd.com/read/27884749/celecoxib-exerts-antitumor-effects-in-hl-60-acute-leukemia-cells-and-inhibits-autophagy-by-affecting-lysosome-function
#3
Ying Lu, Xiang-Fu Liu, Ting-Rong Liu, Rui-Fang Fan, Yi-Chuan Xu, Xiang-Zhong Zhang, Ling-Ling Liu
Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, has been demonstrated to exert antitumor activity in a variety of cancer cells. The underlying mechanism involves inhibition of cell cycle progression and induction of apoptosis. Besides, celecoxib has also been found to induce autophagy in some solid tumor cells. The aim of this study was to investigate the effect of celecoxib on cell proliferation in HL-60 human acute leukemia cells and to explore the potential mechanism. HL-60 cells were exposed to various concentrations of celecoxib and cell viability was evaluated by the MTT assay...
November 21, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27864418/ampk-ulk1-mediated-autophagy-confers-resistance-to-bet-inhibitor-jq1-in-acute-myeloid-leukemia-stem-cells
#4
Ji Eun Jang, Ju In Eom, Hoi Kyung Jeung, June-Won Cheong, Jung Yeon Lee, Jin Seok Kim, Yoo Hong Min
PURPOSE: Bromodomain and extraterminal domain (BET) inhibitors are promising epigenetic agents for the treatment of various subsets of acute myeloid leukemia (AML). However, the resistance of leukemia stem cells (LSCs) to BET inhibitors remains a major challenge. In this study, we evaluated the mechanisms underlying LSC resistance to the BET inhibitor JQ1. EXPERIMENTAL DESIGN: We evaluated the levels of apoptosis and autophagy induced by JQ1 in LSC-like leukemia cell lines and primary CD34(+)CD38(-) leukemic blasts obtained from AML cases with normal karyotype without recurrent mutations...
November 18, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27853367/caveolin-1-contributes-to-realgar-nanoparticle-therapy-in-human-chronic-myelogenous-leukemia-k562-cells
#5
Dan Shi, Yan Liu, Ronggang Xi, Wei Zou, Lijun Wu, Zhiran Zhang, Zhongyang Liu, Chao Qu, Baoli Xu, Xiaobo Wang
Chronic myelogenous leukemia (CML) is characterized by the t(9;22) (q34;q11)-associated Bcr-Abl fusion gene, which is an essential element of clinical diagnosis. As a traditional Chinese medicine, realgar has been widely used for the treatment of various diseases for >1,500 years. Inspired by nano-drug, realgar nanoparticles (NPs) have been prepared with an average particle size of <100 nm in a previous work. Compared with coarse realgar, the realgar NPs have higher bioavailability. As a principal constituent protein of caveolae, caveolin-1 (Cav-1) participates in regulating various cellular physiological and pathological processes including tumorigenesis and tumor development...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27852045/different-bcr-abl-protein-suppression-patterns-as-a-converging-trait-of-chronic-myeloid-leukemia-cell-adaptation-to-energy-restriction
#6
Silvia Bono, Matteo Lulli, Vito Giuseppe D'Agostino, Federico Di Gesualdo, Rosa Loffredo, Maria Grazia Cipolleschi, Alessandro Provenzani, Elisabetta Rovida, Persio Dello Sbarba
BCR/Abl protein drives the onset and progression of Chronic Myeloid Leukemia (CML). We previously showed that BCR/Abl protein is suppressed in low oxygen, where viable cells retain stem cell potential. This study addressed the regulation of BCR/Abl protein expression under oxygen or glucose shortage, characteristic of the in vivo environment where cells resistant to tyrosine kinase inhibitors (TKi) persist. We investigated, at transcriptional, translational and post-translational level, the mechanisms involved in BCR/Abl suppression in K562 and KCL22 CML cells...
November 12, 2016: Oncotarget
https://www.readbyqxmd.com/read/27848186/dasatinib-induces-autophagy-in-mice-with-bcr-abl-positive-leukemia
#7
Makiko Morita, Yoko Nishinaka, Itaru Kato, Satoshi Saida, Hidefumi Hiramatsu, Yasuhiko Kamikubo, Toshio Heike, Tatsutoshi Nakahata, Souichi Adachi
Dasatinib, a second-generation tyrosine kinase inhibitor, is a highly effective treatment for Bcr-Abl-positive leukemia. However, the mechanism by which dasatinib induces cell death is unclear, particularly in vivo. Autophagy is a lysosomal degradation mechanism essential for cell survival and differentiation. Autophagy also protects cells from the effects of drugs, including those used to treat leukemia. Here, we report that dasatinib induces autophagy in Bcr-Abl-positive leukemia cell lines and further show the induction of autophagy in an immunodeficient mouse model of human Bcr-Abl-positive leukemia with central nervous system (CNS) infiltration...
November 15, 2016: International Journal of Hematology
https://www.readbyqxmd.com/read/27821800/synergistic-effects-of-selective-inhibitors-targeting-the-pi3k-akt-mtor-pathway-or-nup214-abl1-fusion-protein-in-human-acute-lymphoblastic-leukemia
#8
Carolina Simioni, Simona Ultimo, Alberto M Martelli, Giorgio Zauli, Daniela Milani, James A McCubrey, Silvano Capitani, Luca M Neri
Philadelphia chromosome-positive (Ph+) Acute Lymphoblastic Leukemia (ALL) accounts for 25-30% of adult ALL and its incidence increases with age in adults >40 years old. Irrespective of age, the ABL1 fusion genes are markers of poor prognosis and amplification of the NUP214-ABL1 oncogene can be detected mainly in patients with T-ALL. T cell malignancies harboring the ABL1 fusion genes are sensitive to many cytotoxic agents, but up to date complete remissions have not been achieved. The PI3K/Akt/mTOR signaling pathway is often activated in leukemias and plays a crucial role in leukemogenesis...
November 3, 2016: Oncotarget
https://www.readbyqxmd.com/read/27817185/pharmacologic-inhibition-of-autophagy-sensitizes-human-acute-leukemia-jurkat-t-cells-to-acacetin-induced-apoptosis
#9
Ji Young Lee, Do Youn Jun, Ki Yun Kim, Eun Ji Ha, Mi Hee Woo, Jee Youn Ko, Young Ho Yun, In-Seok Oh, Young Ho Kim
Exposure of Jurkat T cell clone (J/Neo cells) to acacetin (5,7-dihydroxy-4'-methoxyflavone), which is present in barnyard millet [Echinochloa esculenta (A. Braun)] grains, resulted in cytotoxicity, accumulation of apoptotic sub-G1 cells, Bak activation, loss of mitochondrial membrane potential (Δψm), activation of caspase-9 and caspase-3, cleavage of poly (ADP-ribose) polymerase (PARP), and FITC-Annexin V-stainable phosphatidylserine exposure on the external surface of the cytoplasmic membrane without accompanying necrosis...
November 4, 2016: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27797294/targeting-autophagy-to-overcome-chemoresistance-in-acute-myleogenous-leukemia
#10
Sujan Piya, Michael Andreeff, Gautam Borthakur
Therapeutic inhibition of macroautophagy/autophagy is expected to increase chemosensitivity of cancers and alter tumor-stroma interdependence. The hypoxic, metabolically challenged bone marrow microenvironment confers chemoresistance to leukemia cells. The impact of autophagy inhibition in the context of microenvironment-mediated resistance in leukemia is less explored. Our recent studies demonstrated that co-culture of acute myelogenous leukemia (AML) cells with marrow-derived mesenchymal stromal cells (MSC) induces autophagy in AML cells and increases resistance to genotoxic agents (cytarabine and idarubicin)...
October 31, 2016: Autophagy
https://www.readbyqxmd.com/read/27773925/complete-mutational-spectrum-of-the-autophagy-interactome-a-novel-class-of-tumor-suppressor-genes-in-myeloid-neoplasms
#11
V Visconte, B Przychodzen, Y Han, S T Nawrocki, S Thota, K R Kelly, B J Patel, C Hirsch, A S Advani, H E Carraway, M A Sekeres, J P Maciejewski, J S Carew
Leukemia accepted article preview online, 24 October 2016. doi:10.1038/leu.2016.295.
October 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27761809/detection-of-autophagy-induction-after-hdac-inhibitor-treatment-in-leukemic-cells
#12
Anja Göder, Nisintha Mahendrarajah, Oliver H Krämer
Autophagy is a lysosome-dependent, intracellular pathway for the recycling of cellular components. It plays a pivotal role in both cancer development and the response to chemotherapy. Here we describe how autophagy can be monitored in living cells by flow cytometry using the cationic amphiphilic tracer dye Cyto-ID(®) Green. The detection of autophagy induction in the human leukemia cell line K562 after the treatment with the HDAC class I inhibitor MS-275 serves as an example for this approach.
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27744427/role-of-beclin-1-mediated-autophagy-in-the-survival-of-pediatric-leukemia-cells
#13
Xiaoli Wu, Xuefeng Feng, Xiaoqing Zhao, Futian Ma, Na Liu, Hongming Guo, Chaonan Li, Huan Du, Baoxi Zhang
BACKGROUND/AIMS: Acute and chronic leukemia are severe malignant cancers worldwide, and can occur in pediatric patients. Since bone marrow cell transplantation is seriously limited by the availability of the immune-paired donor sources, the therapy for pediatric leukemia (PL) remains challenging. Autophagy is essential for the regulation of cell survival in the harsh environment. However, the role of autophagy in the survival of PL cells under the oxidative stress, e.g. chemotherapy, remain ill-defined...
October 17, 2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27740626/the-lncrna-hotairm1-regulates-the-degradation-of-pml-rara-oncoprotein-and-myeloid-cell-differentiation-by-enhancing-the-autophagy-pathway
#14
Zhen-Hua Chen, Wen-Tao Wang, Wei Huang, Ke Fang, Yu-Meng Sun, Shu-Rong Liu, Xue-Qun Luo, Yue-Qin Chen
Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are of great importance in different cell contexts. However, only a very small number of lncRNAs have been experimentally validated and functionally annotated during human hematopoiesis. Here, we report an lncRNA, HOTAIRM1, which is associated with myeloid differentiation and has pivotal roles in the degradation of oncoprotein PML-RARA and in myeloid cell differentiation by regulating autophagy pathways. We first revealed that HOTAIRM1 has different variants that are expressed at different levels in cells and that the expression pattern of HOTAIRM1 is closely related to that of the PML-RARA oncoprotein in acute promyelocytic leukemia (APL) patients...
October 14, 2016: Cell Death and Differentiation
https://www.readbyqxmd.com/read/27732946/autophagy-mediates-proteolysis-of-npm1-and-hexim1-and-sensitivity-to-bet-inhibition-in-aml-cells
#15
Min Huang, Jacqueline S Garcia, Daniel Thomas, Li Zhu, Le Xuan Truong Nguyen, Steven M Chan, Ravindra Majeti, Bruno C Medeiros, Beverly S Mitchell
The mechanisms underlying activation of the BET pathway in AML cells remain poorly understood. We have discovered that autophagy is activated in acute leukemia cells expressing mutant nucleophosmin 1 (NPMc+) or MLL-fusion proteins. Autophagy activation results in the degradation of NPM1 and HEXIM1, two negative regulators of BET pathway activation. Inhibition of autophagy with pharmacologic inhibitors or through knocking down autophagy-related gene 5 (Atg5) expression increases the expression of both NPM1 and HEXIM1...
October 6, 2016: Oncotarget
https://www.readbyqxmd.com/read/27722780/n-acetylcysteine-attenuates-intrauterine-growth-retardation-induced-hepatic-damage-in-suckling-piglets-by-improving-glutathione-synthesis-and-cellular-homeostasis
#16
Hao Zhang, Weipeng Su, Zhixiong Ying, Yueping Chen, Le Zhou, Yue Li, Jingfei Zhang, Lili Zhang, Tian Wang
PURPOSE: The objective of the present study was to test the hypothesis that N-acetylcysteine (NAC) may play beneficial roles against intrauterine growth retardation (IUGR)-induced hepatic damage in suckling piglets. METHODS: Fourteen IUGR and seven normal birth weight (NBW) neonatal male piglets were selected. Piglets were weaned at 7 days of postnatal age and fed the control formula milk (NBW-CON and IUGR-CON groups) or the control formula milk supplemented with 1...
October 8, 2016: European Journal of Nutrition
https://www.readbyqxmd.com/read/27698385/photodynamic-n-tio2-nanoparticle-treatment-induces-controlled-ros-mediated-autophagy-and-terminal-differentiation-of-leukemia-cells
#17
Mohammad Amin Moosavi, Maryam Sharifi, Soroush Moasses Ghafary, Zahra Mohammadalipour, Alireza Khataee, Marveh Rahmati, Sadaf Hajjaran, Marek J Łos, Thomas Klonisch, Saeid Ghavami
In this study, we used nitrogen-doped titanium dioxide (N-TiO2) NPs in conjugation with visible light, and show that both reactive oxygen species (ROS) and autophagy are induced by this novel NP-based photodynamic therapy (PDT) system. While well-dispersed N-TiO2 NPs (≤100 μg/ml) were inert, their photo-activation with visible light led to ROS-mediated autophagy in leukemia K562 cells and normal peripheral lymphocytes, and this increased in parallel with increasing NP concentrations and light doses. At a constant light energy (12 J/cm(2)), increasing N-TiO2 NP concentrations increased ROS levels to trigger autophagy-dependent megakaryocytic terminal differentiation in K562 cells...
October 4, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27689330/interconnections-between-apoptotic-and-autophagic-pathways-during-thiopurine-induced-toxicity-in-cancer-cells-the-role-of-reactive-oxygen-species
#18
Wiem Chaabane, Malin Lindqvist Appell
Thiopurines (azathioprine, 6-mercaptopurine and 6-thioguanine) are a class of genotoxic drugs extensively used in the treatment of various illnesses including leukemia. Their underlying molecular mechanism of action involves the activation of apoptosis and autophagy but remains widely unclear. Here we present evidence that autophagy induction by thiopurines is a survival mechanism that antagonizes apoptosis and is involved in degrading damaged mitochondria through mitophagy. On the other hand, apoptosis is the main cell death mechanism by thiopurines as its inhibition prohibited cell death...
September 28, 2016: Oncotarget
https://www.readbyqxmd.com/read/27663133/novel-insights-into-pml-dependent-oncosuppression
#19
Lorenzo Galluzzi
At odds with its nuclear counterpart, extranuclear promyelocytic leukemia constitutively inhibits autophagy, hence limiting cancer progression. These data raise the interesting possibility that some tumor suppressors have become specialized to operate at multiple subcellular compartments for counteracting different aspects of the oncogenic process.
December 2016: Trends in Cell Biology
https://www.readbyqxmd.com/read/27658567/cytoprotective-effect-of-autophagy-on-phagocytosis-of-apoptotic-cells-by-macrophages
#20
Pei Zhou, Yu-Zhen Tan, Hai-Jie Wang, Ting Li, Tao He, Ying Yu, Jian Zhang, Dan Zhang
Clearance of the apoptotic cells by phagocytes plays pivotal roles in maintenance of tissue homeostasis, promotion of immunological tolerance and anti-inflammatory response. Recent studies show that autophagy is involved in phagocytosis of the apoptotic cells. However, contribution of autophagy to phagocytosis of the apoptotic cells by macrophages is not clearly defined. Here, we assessed cytoprotective effect of autophagy on clearance of the apoptotic cells. Apoptosis of murine splenic lymphocytes and human T-cell leukemia cells was induced with cyclophosphamide...
September 20, 2016: Experimental Cell Research
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