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promyelocytic leukemia protein

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https://www.readbyqxmd.com/read/28427227/high-dose-ascorbate-and-arsenic-trioxide-selectively-kill-acute-myeloid-leukemia-and-acute-promyelocytic-leukemia-blasts-in-vitro
#1
Nélida I Noguera, Elvira Pelosi, Daniela F Angelini, Maria Liliana Piredda, Gisella Guerrera, Eleonora Piras, Luca Battistini, Lauretta Massai, Anna Berardi, Gianfranco Catalano, Laura Cicconi, Germana Castelli, Agnese D'Angiò, Luca Pasquini, Grazia Graziani, Giuseppe Fioritoni, Maria Teresa Voso, Domenico Mastrangelo, Ugo Testa, Francesco Lo-Coco
The use of high-dose ascorbate (ASC) for the treatment of human cancer has been attempted several decades ago and has been recently revived by several in vitro and in vivo studies in solid tumors. We tested the cytotoxic effects of ASC, alone or in combination with arsenic trioxide (ATO) in acute myeloid leukemia (AML) and acute promyelocytic leukemia (APL). Leukemic cell lines and primary blasts from AML and APL patients were treated with graded concentrations of ASC, alone or in association with standard concentration (1 μM) of ATO...
March 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28425984/withaferin-a-kills-cancer-cells-with-and-without-telomerase-chemical-computational-and-experimental-evidences
#2
Yue Yu, Shashank P Katiyar, Durai Sundar, Zeenia Kaul, Eijiro Miyako, Zhenya Zhang, Sunil C Kaul, Roger R Reddel, Renu Wadhwa
Maintenance of telomere length is the most consistent attribute of cancer cells. Tightly connected to their capacity to overcome replicative mortality, it is achieved either by activation of telomerase or an Alternative mechanism of Lengthening of Telomeres (ALT). Disruption of either of these mechanisms has been shown to induce DNA damage signalling leading to senescence or apoptosis. Telomerase inhibitors are considered as potential anticancer drugs but are ineffective for ALT cancers (~15% of all cancers)...
April 20, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28401935/unique-invariant-natural-killer-t-cells-promote-intestinal-polyps-by-suppressing-th1-immunity-and-promoting-regulatory-t-cells
#3
Y Wang, S Sedimbi, L Löfbom, A K Singh, S A Porcelli, S L Cardell
CD1d-restricted invariant natural killer T (iNKT) cells are known as potent early regulatory cells of immune responses. Besides the established roles in the regulation of inflammation and autoimmune disease, studies have shown that iNKT cells have important roles in tumor surveillance and the control of tumor metastasis. Here we found that the absence of iNKT cells markedly decreased the total number of intestinal polyps in APC(Min/+) mice, a model for colorectal cancer. Polyp iNKT cells were enriched for interleukin-10 (IL-10)- and IL-17-producing cells, showed a distinct phenotype being CD4(+), NK1...
April 12, 2017: Mucosal Immunology
https://www.readbyqxmd.com/read/28396661/phenotype-of-nk-like-cd8-t-cells-with-innate-features-in-humans-and-their-relevance-in-cancer-diseases
#4
Alice Barbarin, Emilie Cayssials, Florence Jacomet, Nicolas Gonzalo Nunez, Sara Basbous, Lucie Lefèvre, Myriam Abdallah, Nathalie Piccirilli, Benjamin Morin, Vincent Lavoue, Véronique Catros, Eliane Piaggio, André Herbelin, Jean-Marc Gombert
Unconventional T cells are defined by their capacity to respond to signals other than the well-known complex of peptides and major histocompatibility complex proteins. Among the burgeoning family of unconventional T cells, innate-like CD8(+) T cells in the mouse were discovered in the early 2000s. This subset of CD8(+) T cells bears a memory phenotype without having encountered a foreign antigen and can respond to innate-like IL-12 + IL-18 stimulation. Although the concept of innate memory CD8(+) T cells is now well established in mice, whether an equivalent memory NK-like T-cell population exists in humans remains under debate...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28392218/promyelocytic-leukemia-protein-is-an-essential-regulator-of-stem-cell-pluripotency-and-somatic-cell-reprogramming
#5
Christiana Hadjimichael, Konstantina Chanoumidou, Christoforos Nikolaou, Antonios Klonizakis, Gesthimani-Ioanna Theodosi, Takis Makatounakis, Joseph Papamatheakis, Androniki Kretsovali
Promyelocytic leukemia protein (PML), the main constituent of PML nuclear bodies, regulates various physiological processes in different cell types. However, little is known about its functions in embryonic stem cells (ESC). Here, we report that PML contributes to ESC self-renewal maintenance by controlling cell-cycle progression and sustaining the expression of crucial pluripotency factors. Transcriptomic analysis and gain- or loss-of-function approaches showed that PML-deficient ESC exhibit morphological, metabolic, and growth properties distinct to naive and closer to the primed pluripotent state...
March 30, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28369036/chromatin-remodeling-factor-smarcd2-regulates-transcriptional-networks-controlling-differentiation-of-neutrophil-granulocytes
#6
Maximilian Witzel, Daniel Petersheim, Yanxin Fan, Ehsan Bahrami, Tomas Racek, Meino Rohlfs, Jacek Puchałka, Christian Mertes, Julien Gagneur, Christoph Ziegenhain, Wolfgang Enard, Asbjørg Stray-Pedersen, Peter D Arkwright, Miguel R Abboud, Vahid Pazhakh, Graham J Lieschke, Peter M Krawitz, Maik Dahlhoff, Marlon R Schneider, Eckhard Wolf, Hans-Peter Horny, Heinrich Schmidt, Alejandro A Schäffer, Christoph Klein
We identify SMARCD2 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily D, member 2), also known as BAF60b (BRG1/Brahma-associated factor 60b), as a critical regulator of myeloid differentiation in humans, mice, and zebrafish. Studying patients from three unrelated pedigrees characterized by neutropenia, specific granule deficiency, myelodysplasia with excess of blast cells, and various developmental aberrations, we identified three homozygous loss-of-function mutations in SMARCD2...
April 3, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28358373/myogenic-differentiation-triggers-pml-nuclear-body-loss-and-daxx-relocalization-to-chromocentres
#7
Jayme Salsman, Lindsy M Rapkin, Nandini N Margam, Roy Duncan, David P Bazett-Jones, Graham Dellaire
The promyelocytic leukemia protein (PML) is expressed in most normal human tissues and forms nuclear bodies (NBs) that have roles in gene regulation and cellular processes such as DNA repair, cell cycle control, and cell fate decisions. Using murine C2C12 myoblasts, we demonstrate that activation of skeletal muscle differentiation results in loss of PML and PML NBs prior to myotube fusion. Myotube formation was associated with marked chromatin reorganization and the relocalization of DAXX from PML NBs to chromocentres...
March 30, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28341773/pml-protein-organizes-heterochromatin-domains-where-it-regulates-histone-h3-3-deposition-by-atrx-daxx
#8
Erwan Delbarre, Kristina Ivanauskiene, Jane Spirkoski, Akshay Shah, Kristin Vekterud, Jan Øivind Moskaug, Stig Ove Bøe, Lee Wong, Thomas Küntziger, Philippe Collas
Maintenance of chromatin homeostasis involves proper delivery of histone variants to the genome. The interplay between different chaperones regulating the supply of histone variants to distinct chromatin domains is largely undeciphered. We report here a role of promyelocytic leukemia (PML) protein in routing histone variant H3.3 to chromatin and in the organization of megabase-size heterochromatic PML-associated domains which we call PADs. Loss of PML alters the heterochromatic state of PADs by shifting the histone H3 methylation balance from K9me3 to K27me3...
March 24, 2017: Genome Research
https://www.readbyqxmd.com/read/28341738/higher-hopx-expression-is-associated-with-distinct-clinical-and-biological-features-and-predicts-poor-prognosis-in-de-novo-acute-myeloid-leukemia
#9
Chien-Chin Lin, Yueh-Chwen Hsu, Yi-Hung Li, Yuan-Yeh Kuo, Hsin-An Hou, Keng-Hsueh Lan, Tsung-Chih Chen, Yi-Shiuan Tzeng, Yi-Yi Kuo, Chein-Jun Kao, Po-Han Chuang, Mei-Hsuan Tseng, Yu-Chiao Chiu, Wen-Chien Chou, Hwei-Fang Tien
Homeodomain-only protein homeobox (HOPX) is the smallest homeodomain protein. It was regarded as a stem cell marker in several non-hematopoietic systems. While the prototypic homeobox genes such as HOX family have been well characterized in acute myeloid leukemia, the clinical and biological implications of HOPX in the disease remain unknown. Thus we analyzed HOPX and global gene expression patterns in 347 newly diagnosed de novo acute myeloid leukemia patients in our institute. We found that higher HOPX expression was closely associated with older age, higher platelet counts, lower white blood cell counts, lower lactate dehydrogenase levels, and mutations in RUNX1, IDH2, ASXL1, and DNMT3A, but negatively associated with acute promyelocytic leukemia, favorable karyotypes, CEBPA double mutations and NPM1 mutation...
March 24, 2017: Haematologica
https://www.readbyqxmd.com/read/28340577/gene-and-protein-analysis-reveals-that-p53-pathway-is-functionally-inactivated-in-cytogenetically-normal-acute-myeloid-leukemia-and-acute-promyelocytic-leukemia
#10
Julia Abramowitz, Tzahi Neuman, Riki Perlman, Dina Ben-Yehuda
BACKGROUND: Mechanisms that inactivate the p53 pathway in Acute Myeloid Leukemia (AML), other than rare mutations, are still not well understood. METHODS: We performed a bioinformatics study of the p53 pathway function at the gene expression level on our collection of 1153 p53-pathway related genes. Publically available Affymetrix data of 607 de-novo AML patients at diagnosis were analyzed according to the patients cytogenetic, FAB and molecular mutations subtypes...
March 24, 2017: BMC Medical Genomics
https://www.readbyqxmd.com/read/28335578/exploring-the-antitumor-mechanism-of-high-dose-cytarabine-through-the-metabolic-perturbations-of-ribonucleotide-and-deoxyribonucleotide-in-human-promyelocytic-leukemia-hl-60-cells
#11
Zheng Li, Jian-Ru Guo, Qian-Qian Chen, Cai-Yun Wang, Wei-Jia Zhang, Mei-Cun Yao, Wei Zhang
Despite the apparent clinical benefits of high-dose cytarabine (Ara-C) over lower dose Ara-C in acute myeloid leukemia (AML) therapy, the mechanism behind high-dose Ara-C therapy remains uncertain. In this study, a LC-MS-based method was carried out to investigate the metabolic alteration of ribonucleotide and deoxyribonucleotide in human promyelocytic leukemia cells (HL-60) after treatment with Ara-C to reveal its antitumor mechanism. The metabolic results revealed that four nucleotides (ATP, ADP, CDP, and dCTP) could be used as potential biomarkers indicating the benefit of high-dose Ara-C over lower dose Ara-C treatment...
March 21, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28332630/pml-nuclear-bodies-contribute-to-the-basal-expression-of-the-mtor-inhibitor-ddit4
#12
Jayme Salsman, Alex Stathakis, Ellen Parker, Dudley Chung, Livia E Anthes, Kara L Koskowich, Sara Lahsaee, Daniel Gaston, Kimberly R Kukurba, Kevin S Smith, Ian C Chute, Daniel Léger, Laura D Frost, Stephen B Montgomery, Stephen M Lewis, Christopher Eskiw, Graham Dellaire
The promyelocytic leukemia (PML) protein is an essential component of PML nuclear bodies (PML NBs) frequently lost in cancer. PML NBs coordinate chromosomal regions via modification of nuclear proteins that in turn may regulate genes in the vicinity of these bodies. However, few PML NB-associated genes have been identified. PML and PML NBs can also regulate mTOR and cell fate decisions in response to cellular stresses. We now demonstrate that PML depletion in U2OS cells or TERT-immortalized normal human diploid fibroblasts results in decreased expression of the mTOR inhibitor DDIT4 (REDD1)...
March 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317833/regulation-of-nf-%C3%AE%C2%BAb-by-pml-and-pml-rar%C3%AE
#13
Abrar Ahmed, Xiaochun Wan, Izaskun Mitxitorena, Andrew J Lindsay, Pier Paolo Pandolfi, Mary W McCaffrey, Karen Keeshan, Youhai H Chen, Ruaidhrí J Carmody
Promyelocytic Leukemia (PML) is a nuclear protein that forms sub-nuclear structures termed nuclear bodies associated with transcriptionally active genomic regions. PML is a tumour suppressor and regulator of cell differentiation. We demonstrate that PML promotes TNFα-induced transcriptional responses by promoting NF-κB activity. TNFα-treated PML(-/-) cells show normal IκBα degradation and NF-κB nuclear translocation but significantly reduced NF-κB DNA binding and phosphorylation of NF-κB p65. We also demonstrate that the PML retinoic acid receptor-α (PML-RARα) oncofusion protein, which causes acute promyelocytic leukemia, inhibits TNFα induced gene expression and phosphorylation of NF-κB...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28304015/sodium-periodate-mediated-conjugation-of-harringtonine-enabling-the-production-of-a-highly-specific-monoclonal-antibody-and-the-development-of-a-sensitive-quantitative-analysis-method
#14
Seiichi Sakamoto, Gorawit Yusakul, Yumi Tsuneura, Waraporn Putalun, Kazuteru Usui, Tomofumi Miyamoto, Hiroyuki Tanaka, Satoshi Morimoto
Harringtonine (HT) is a promising natural product that is mainly isolated from plants of the genus Cephalotaxus. Due to its remarkable antileukemic activities, HT has been utilized clinically in China for the treatment of acute promyelocytic leukemia (APL). No antibody that recognizes free HT has been reported to date due to the difficulty of preparing antigen conjugates in which haptens bind to a carrier protein. To overcome this difficulty, we focused on sodium periodate (NaIO4), which catalyzes unique oxidative reactions; the resulting conjugates enabled the production of a highly specific monoclonal antibody (MAb) against HT (MAb 1D2) and the establishment of an indirect competitive enzyme-linked immunosorbent assay (icELISA) for the determination of HT...
March 17, 2017: Analyst
https://www.readbyqxmd.com/read/28303135/a-human-lin-cd123-cd127-low-population-endowed-with-ilc-features-and-migratory-capabilities-contributes-to-immunopathological-hallmarks-of-psoriasis
#15
Luz María Mora-Velandia, Octavio Castro-Escamilla, Andrés González Méndez, Cristina Aguilar-Flores, Martha Velázquez-Avila, María Isabel Tussié-Luna, Juan Téllez-Sosa, César Maldonado-García, Fermín Jurado-Santacruz, Eduardo Ferat-Osorio, Jesus Martínez-Barnetche, Rosana Pelayo, Laura C Bonifaz
Innate lymphoid cells (ILC) are members of a heterogeneous family with a lymphoid origin that mimics the T helper (Th) cytokine profile. ILC are involved in early effector cytokine-mediated responses during infections in peripheral tissues. ILC also play an important role in chronic skin inflammatory diseases, including psoriasis. Although classical ILC express CD127, it has been recently reported that the presence of non-classical CD127(-) ILC populations and an early ILC precursor (EILP) CD127(low). ILC development has predominately been investigated in mouse models...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28298075/inducing-cell-proliferative-prevention-in-human-acute-promyelocytic-leukemia-by-mir-182-inhibition-through-modulation-of-casp9-expression
#16
Mahdi Fasihi-Ramandi, Abbas Moridnia, Ali Najafi, Mohammadreza Sharifi
MicroRNAs (miRNAs) are one class of endogenous non-coding RNAs that involved in post-transcriptional regulation of the gene. MiRNAs through interaction with messenger RNA (mRNA) involved in several biological processes such as cell cycle, differentiation, growth, metabolism, aging and apoptosis. MiRNAs may act as an oncogene or a tumor suppressor via up or down regulation in cancerous cells. MiR-182 located in a miR-183/-96/-182 cluster, this is the highly conserved cluster to have an important role in cancer development and tumorigenesis...
March 11, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28286608/meta-analysis-of-gene-expression-profiles-in-acute-promyelocytic-leukemia-reveals-involved-pathways
#17
Mahdi Jalili, Ali Salehzadeh-Yazdi, Saeed Mohammadi, Marjan Yaghmaie, Ardeshir Ghavamzadeh, Kamran Alimoghaddam
Background: Acute promyelocytic leukemia (APL) is a unique subtype of acute leukemia. APL is a curable disease; however, drug resistance, early mortality, disease relapse and treatment-related complications remain challenges in APL patient management. One issue underlying these challenges is that the molecular mechanisms of the disease are not sufficiently understood. Materials and Methods: In this study, we performed a meta-analysis of gene expression profiles derived from microarray experiments and explored the background of disease by functional and pathway analysis...
January 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/28250117/the-nd10-component-promyelocytic-leukemia-protein-acts-as-an-e3-ligase-for-sumoylation-of-the-major-immediate-early-protein-ie1-of-human-cytomegalovirus
#18
Nina Reuter, Eva-Maria Schilling, Myriam Scherer, Regina Müller, Thomas Stamminger
Previous studies identified the nuclear domain 10 (ND10) components PML, hDaxx, and Sp100 as factors of an intrinsic immune response against human cytomegalovirus (HCMV). This antiviral function of ND10, however, is antagonized by viral effector proteins like IE1p72, which induces a dispersal of ND10. Furthermore, we have shown that both major immediate-early proteins of HCMV, IE1p72 and IE2p86, transiently co-localize with ND10 subnuclear structures and undergo modification by the covalent attachment of SUMO...
March 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28241849/metformin-potentiates-the-effect-of-arsenic-trioxide-suppressing-intrahepatic-cholangiocarcinoma-roles-of-p38-mapk-erk3-and-mtorc1
#19
Sunbin Ling, Haiyang Xie, Fan Yang, Qiaonan Shan, Haojiang Dai, Jianyong Zhuo, Xuyong Wei, Penghong Song, Lin Zhou, Xiao Xu, Shusen Zheng
BACKGROUND: Arsenic trioxide (ATO) is commonly used in the treatment of acute promyelocytic leukemia (APL), but does not benefit patients with solid tumors. When combined with other agents or radiation, ATO showed treatment benefits with manageable toxicity. Previously, we reported that metformin amplified the inhibitory effect of ATO on intrahepatic cholangiocarcinoma (ICC) cells more significantly than other agents. Here, we investigated the chemotherapeutic sensitization effect of metformin in ATO-based treatment in ICC in vitro and in vivo and explored the underlying mechanisms...
February 28, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28239645/pml-promotes-metastasis-of-triple-negative-breast-cancer-through-transcriptional-regulation-of-hif1a-target-genes
#20
Manfredi Ponente, Letizia Campanini, Roberto Cuttano, Andrea Piunti, Giacomo A Delledonne, Nadia Coltella, Roberta Valsecchi, Alessandra Villa, Ugo Cavallaro, Linda Pattini, Claudio Doglioni, Rosa Bernardi
Elucidating the molecular basis of tumor metastasis is pivotal for eradicating cancer-related mortality. Triple-negative breast cancer (TNBC) encompasses a class of aggressive tumors characterized by high rates of recurrence and metastasis, as well as poor overall survival. Here, we find that the promyelocytic leukemia protein PML exerts a prometastatic function in TNBC that can be targeted by arsenic trioxide. We found that, in TNBC patients, constitutive HIF1A activity induces high expression of PML, along with a number of HIF1A target genes that promote metastasis at multiple levels...
February 23, 2017: JCI Insight
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