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https://www.readbyqxmd.com/read/28734155/activation-of-mtor-is-involved-in-anti-%C3%AE-2gpi-%C3%AE-2gpi-induced-expression-of-tissue-factor-and-il-8-in-monocytes
#1
Longfei Xia, Hong Zhou, Ting Wang, Yachao Xie, Ting Wang, Xiaoyan Wang, Jinchuan Yan
Previous study has demonstrated that activation of the mammalian target of rapamycin (mTOR) pathway in endothelial cells (ECs) results in the formation of chronic vascular lesions associated with antiphospholipid syndrome (APS). In addition, it has been shown that stimulation of monocytes and ECs by antiphospholipid antibodies (aPL) leads to a prothrombotic and proinflammatory state and up-regulated expression of tissue factor (TF) and inflammatory cytokines. However, the role of mTOR in pathogenic mechanisms of APS remains largely unexplored...
June 1, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28730166/impact-of-chromosomal-rearrangement-upon-dna-methylation-patterns-in-leukemia
#2
Hyang-Min Byun, Shahrooz Eshaghian, Dan Douer, Jonathen Trent, Guillermo Garcia-Manero, Ravi Bhatia, Kim Siegmund, Allen S Yang
Genomic instability, including genetic mutations and chromosomal rearrangements, can lead to cancer development. Aberrant DNA methylation occurs commonly in cancer cells. The aim of this study is to determine the effects of a specific chromosomal lesion the BCR-ABL translocation t(9:22), in establishing DNA methylation profiles in cancer. Materials and methods We compared DNA methylation of 1,505 selected promoter CpGs in chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL) with and without the Philadelphia chromosome t(9:22), CD34+ hematopoietic stem cells transfected with BCR-ABL, and other tumors without BCR-ABL (acute promyelocytic leukemia (APL) and gastrointestinal stromal tumors (GIST)...
2017: Open Medicine (Warsaw, Poland)
https://www.readbyqxmd.com/read/28729405/super-enhancer-analysis-defines-novel-epigenomic-subtypes-of-non-apl-aml-including-an-rar%C3%AE-dependency-targetable-by-sy-1425-a-potent-and-selective-rar%C3%AE-agonist
#3
Michael R McKeown, M Ryan Corces, Matthew L Eaton, Chris Fiore, Emily Lee, Jeremy T Lopez, Mei Wei Chen, Darren Smith, Steven M Chan, Julie L Koenig, Kathryn Austgen, Matt G Guenther, David A Orlando, Jakob Lovén, Christian C Fritz, Ravindra Majeti
We characterized the enhancer landscape of 66 AML patients, identifying 6 novel subgroups and their associated regulatory loci. These subgroups are defined by their super-enhancer (SE) maps, orthogonal to somatic mutations, and are associated with distinct leukemic cell states. Examination of transcriptional drivers for these epigenomic subtypes uncovers a subset of patients with a particularly strong super-enhancer at the retinoic acid receptor alpha (RARA) gene locus. Presence of a RARA SE and concomitant high levels of RARA mRNA predisposes cell lines and ex vivo models to exquisite sensitivity to a selective agonist of RARα, SY-1425 (tamibarotene)...
July 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28728511/anticoagulation-withdrawal-in-antiphospholipid-syndrome-a-retrospective-matched-control-study
#4
C M Yelnik, G Urbanski, E Drumez, C Caron, H Maillard, S Morell-Dubois, S Dubucquoi, D Launay, E Hachulla, P Y Hatron, A Duhamel, M Lambert
Background/Purpose Long-term anticoagulation is the standard treatment for thrombotic antiphospholipid syndrome (APS). However, in daily practice, the question of withdrawing anticoagulation may arise, without any evidence-based recommendations. This study aimed to assess outcomes in APS patients after anticoagulation withdrawal. Methods Thrombotic APS patients followed in our centre, whose anticoagulation was withdrawn after APS diagnosis, were retrospectively selected, and were match-controlled with patients under anticoagulation, based on sex, age, APS clinical phenotype and disease duration...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28727732/incidence-of-thromboembolic-events-in-asymptomatic-carriers-of-iga-anti-%C3%A3-2-glycoprotein-i-antibodies
#5
Carlos Tortosa, Oscar Cabrera-Marante, Manuel Serrano, José A Martínez-Flores, Dolores Pérez, David Lora, Luis Morillas, Estela Paz-Artal, José M Morales, Daniel Pleguezuelo, Antonio Serrano
BACKGROUND: The antiphospholipid syndrome (APS) is defined by simultaneous presence of vascular clinical events and antiphospholipid antibodies (aPL). The aPL considered as diagnostics are lupus anticoagulant and antibodies anticardiolipin (aCL) and anti-ß2 glycoprotein-I (aB2GP1). During recent years, IgA aB2GP1 antibodies have been associated with thrombotic events both in patients positive, and mainly negative for other aPL, however its value as a pro-thrombotic risk-factor in asymptomatic patients has not been well defined...
2017: PloS One
https://www.readbyqxmd.com/read/28722470/novel-potent-inhibitors-of-the-histone-demethylase-kdm1a-lsd1-orally-active-in-a-murine-promyelocitic-leukemia-model
#6
Paolo Trifirò, Anna Cappa, Silvia Brambillasca, Oronza A Botrugno, Maria Rosaria Cera, Roberto Dal Zuffo, Paola Dessanti, Giuseppe Meroni, Florian Thaler, Manuela Villa, Saverio Minucci, Ciro Mercurio, Mario Varasi, Paola Vianello
BACKGROUND: Histone lysine demethylases (KDMs) are well-recognized targets in oncology drug discovery. They function at the post-translation level controlling chromatin conformation and gene transcription. KDM1A is a flavin adenine dinucleotide-dependent amine oxidase, overexpressed in several tumor types, including acute myeloid leukemia, neuroblastoma and non-small-cell lung cancer. Among the many known monoamine oxidase inhibitors screened for KDM1A inhibition, tranylcypromine emerged as a moderately active hit, which irreversibly binds to the flavin adenine dinucleotide cofactor...
July 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28721499/treg-protected-donor-lymphocyte-infusions-a-new-tool-to-address-the-graft-versus-leukemia-effect-in-the-absence-of-graft-versus-host-disease-in-patients-relapsed-after-hsct
#7
Mauro Di Ianni, Paola Olioso, Raffaella Giancola, Stella Santarone, Annalisa Natale, Gabriele Papalinetti, Ida Villanova, Stefano Baldoni, Ambra Di Tommaso, Tiziana Bonfini, Patrizia Accorsi, Paolo Di Bartolomeo
In high-risk acute leukemia patients undergoing haploidentical hematopoietic stem cell transplantation (HSCT), adoptive immunotherapy with T regulatory cells (Tregs) and T conventional cells (Tcons) prevented acute and chronic graft-versus-host disease (GvHD), favored post-transplant immunological reconstitution and was associated with a powerful graft-versus-leukemia (GvL) effect. With a particularly innovative approach, we developed a treatment with a Treg-protected donor lymphocyte infusion (DLI) for patients with early relapse after HSCT and we report here the results obtained in the first patient with APL (M3v) relapsed after a second matched allogeneic HSCT (15% blasts and 75% of donor cells in bone marrow)...
July 18, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28719914/the-significance-of-antibodies-against-domain-i-of-beta-2-glycoprotein-i-in-antiphospholipid-syndrome
#8
Hilde Kelchtermans, Walid Chayouâ, Bas de Laat
The antiphospholipid syndrome (APS) is characterized by vascular thrombosis and/or pregnancy morbidity with the persistent presence of antiphospholipid antibodies (aPLs). Progress is being made in understanding the pathogenesis of the syndrome, but difficulties persist in the identification of patients at risk for thrombosis and/or pregnancy morbidity. Beta-2 glycoprotein I (β2GPI), a plasma protein consisting of five sushi domains, is thought to be the main antigenic target of aPLs. Antibodies recognizing domain I of β2GPI are predominantly present in patients with an elevated risk of thrombosis, whereas antidomain IV/V antibodies are found in nonthrombotic autoimmune diseases...
July 18, 2017: Seminars in Thrombosis and Hemostasis
https://www.readbyqxmd.com/read/28719347/regulatory-effects-of-the-novel-synthesized-indole-3-carbaldehyde-on-expression-of-cell-cycle-genes-a-study-on-cyclin-d-and-p21-expression-by-acute-promylocytic-leukemia-cell-line-nb4
#9
M N Karimabad, M Mahmoodi, A Jafarzadeh, A Darekordi, M R Hajizadeh, H Khorramdelazad, A R Sayadi, S Khanamani Falahati-Pour, G Hassanshahi
A large variety of heterocycles are known to date and among these, indole and pyran rings are of particular interest. The present investigation was aimed to investigate the effects of novel Indole-3-carbaldehyde derivative (NI-3-CD) analogue on growth inhibition of cells and its regulatory effects on expression of cell cycle genes in acute promylocytic leukemia (APL) cell line. NB4 cells were cultured in presence of RPMI1640 medium contained various concentrations of NI-3-CD and basal compound of indole (I3C) (15...
May 20, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28713949/shikonin-suppresses-proliferation-and-induces-apoptosis-in-human-leukemia-nb4-cells-through-modulation-of-mapks-and-c%C3%A2-myc
#10
Zhi-Ling Shan, Liang Zhong, Chu-Lan Xiao, Liu-Gen Gan, Ting Xu, Hao Song, Rong Yang, Liu Li, Bei-Zhong Liu
Acute promyelocytic leukemia (APL) is a special subtype of acute myeloid leukemia that responds to treatment with all‑trans retinoic acid and arsenic trioxide. However, severe side effects and drug resistance limit the effectiveness of these treatments. Hence, new drugs for APL are required urgently. Shikonin, an active naphthoquinone derived from the Chinese medical herb Zi Cao exerts antitumor activity in several cancers. In the present study, the effects of shikonin on proliferation and apoptosis in NB4 cells, as well as related mechanisms were assessed...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28712407/-detection-and-clinical-significance-of-pml-protein-expression-of-acute-promyelocytic-leukemia-cells
#11
Mei Song, Xiumei Wu, Mei Zhang, Pengcheng He
Objective To study the expression patterns of promyelocytic leukemia (PML) protein at different stages of acute promyelocytic leukemia (APL) and investigate the effects that the arsenical, all-trans retinoic acid (ATRA) and chemotherapeutic drugs on PML protein expression patterns. Methods The bone marrow cells of 42 APL patients, NB4 cells and MR2 cells were collected and treated separately with 1 μmol/L arsenic trioxide (As2O3), 1 μmol/L tetra-arsenic tetra-sulfide (As4S4), 1 μmol/L ATRA, 10 mg/L cytosine arabinoside, and 1 mg/L homoharringtonine...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28711674/hplc-hg-afs-determination-of-arsenic-species-in-acute-promyelocytic-leukemia-apl-plasma-and-blood-cells
#12
Meihua Guo, Wenjing Wang, Xin Hai, Jin Zhou
Arsenic trioxide (ATO) has been successfully used in the treatment of acute promyelocytic leukemia (APL). To clarify the arsenic species in APL patients, high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS) and HG-AFS methods were developed and validated to quantify the plasma concentrations of inorganic arsenic (As(III) and As(V)) and methylated metabolites (MMA and DMA), and the total amounts of arsenic in blood cells and plasma. Blood cells and plasma were digested with mixtures of HNO3H2O2 and analyzed by HG-AFS...
July 6, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28705035/the-association-between-abo-blood-types-and-venous-thromboembolism-in-individuals-with-a-positive-antiphospholipid-profile-is-varied-by-sex
#13
M Shusterman, E Golub, W B Mowrey, A Broder
Objectives Although non-O blood type is an established risk factor for venous thromboembolism in the general population, the impact of ABO blood type (ABO) on venous thromboembolism risk in individuals with persistent antiphospholipid antibodies (aPL) has not been studied. We sought to investigate the relationship between ABO and venous thromboembolism in aPL-positive individuals. We also sought to explore potential interactions between ABO and sex or race to determine whether ABO contributes to race or sex differences with respect to the development of venous thromboembolism...
January 1, 2017: Lupus
https://www.readbyqxmd.com/read/28687976/annexin-a2-s100a10-heterotetramer-is-upregulated-by-pml-rar%C3%AE-fusion-protein-and-promotes-plasminogen-dependent-fibrinolysis-and-matrix-invasion-in-acute-promyelocytic-leukemia
#14
Dan Huang, Yan Yang, Jian Sun, Xiaorong Dong, Jiao Wang, Hongchen Liu, Chengquan Lu, Xueyu Chen, Jing Shao, Jinsong Yan
Aberrant expression of annexin A2-S100A10 heterotetramer (AIIt) associated with PML/RARα fusion protein causes lethal hyperfibrinolysis in acute promyelocytic leukemia (APL), but the mechanism is unclear. To facilitate the investigation of regulatory association between ANXA2 and promyelocytic leukemia/retinoic acid receptor α (PML/RARα) fusion protein, this work was performed to determine the transcription start site of ANXA2 promoter with rapid amplification of 5'-cDNA ends analysis. Zinc-induced U937/PR9 cells expressed PML/RARα fusion protein, and resultant increases in ANXA2 transcripts and translational expressions of both ANXA2 and S100A10, while S100A10 transcripts remained constitutive...
July 8, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28686816/first-line-non-criterial-antiphospholipid-antibody-testing-for-the-diagnosis-of-antiphospholipid-syndrome-in-clinical-practice-a-combination-of-anti-beta2-glycoprotein-i-domain-i-and-phosphatidylserine-dependent-antiprothrombin-antibodies
#15
Hiroyuki Nakamura, Kenji Oku, Olga Amengual, Kazumasa Ohmura, Yuichiro Fujieda, Masaru Kato, Toshiyuki Bohgaki, Shinsuke Yasuda, Tatsuya Atsumi
OBJECTIVE: The aim of this study was to assess the value of a combination of anti-beta2-glycoprotein I domain I antibodies (aDI) and phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) tests for the diagnosis of antiphospholipid syndrome (APS). METHODS: This cross-sectional study involved a cohort of the patients who visited our clinic from April 2005 to March 2013. IgG aDI, IgG aPS/PT, and IgM aPS/PT tests, together with criteria-defined antiphospholipid antibodies (aPL) tests, were performed in all patients...
July 7, 2017: Arthritis Care & Research
https://www.readbyqxmd.com/read/28679299/arsenic-trioxide-decreases-the-amount-and-inhibits-the-function-of-regulatory-t-cells-which-may-contribute-to-its-efficacy-in-the-treatment-of-acute-promyelocytic-leukemia
#16
Wen Xu, Xiaoxia Li, Lina Quan, Jiying Yao, Guannan Mu, Jingjie Guo, Yitong Wang
Arsenic trioxide (ATO) exhibits substantial clinical efficacy in the treatment of acute promyelocytic leukemia (APL). Here, we investigated whether ATO exerts its efficacy by affecting regulatory T (Treg) cells. We determined whether ATO treatment influenced the amount and function of purified Treg cells. We also examined the effect of ATO treatment on Treg cells from APL patients. ATO treatment induced apoptosis in purified Treg cells and dampened the inhibition of effector T (Teff) cells proliferation and the secretion of cytokine by Treg cells...
July 6, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28667788/altered-%C3%AE-2-glycoprotein-i-expression-on-microparticles-in-the-presence-of-antiphospholipid-antibodies
#17
Fariborz Mobarrez, Iva Gunnarsson, Elisabet Svenungsson
BACKGROUND: Antiphospholipid antibodies (aPL) together with thrombosis and/or pregnancy morbidities characterize the antiphospholipid syndrome. β2-glycoprotein-I (β2 GPI), the most important antigen for aPL, is a scavenger molecule that specifically binds to phosphatidylserine (PS), expressed on microparticles (MPs). OBJECTIVES: We evaluated β2 GPI-expressing MPs in patients with systemic lupus erythematosus (SLE) stratified for aPL status, and healthy controls...
July 1, 2017: Journal of Thrombosis and Haemostasis: JTH
https://www.readbyqxmd.com/read/28666081/mhc-class-ii-alleles-influence-induction-of-pathogenic-antiphospholipid-antibodies-in-a-thrombosis-mouse-model
#18
Elizabeth Papalardo, Zurina Romay-Penabad, Rohan Willis, Premkumar Christadoss, Ana Laura Carrera-Marin, Elba Reyes-Maldonado, Rajani Rudrangi, Silvana Alfieri-Papalardo, Ethel Garcia-Latorre, Miri Blank, Silvia Pierangeli, Allan R Brasier, Emilio B Gonzalez
OBJECTIVE: Both environmental and genetic factors are important in antiphospholipid antibody(aPL) development in antiphospholipid syndrome(APS). Currently, the only available data on predisposing genetic factors have been obtained from epidemiological studies without mechanistic evidence. Therefore, we studied the influence of Major Histocompatibility Complex Class II(MHC-II) alleles on the production of aPL in an APS mouse model. METHODS: Three groups of mice: MHC-II deficient (MHC-II(-/-) ) mice, MHC-II(-/-) mice transgenic for human DQ6, DQ8 or DR4 alleles and their corresponding wild-type(WT) strains were each immunized, half with human β2 glycoprotein-I(β2 GPI) and the other half with control ovalbumin(OA) protein...
June 30, 2017: Arthritis & Rheumatology
https://www.readbyqxmd.com/read/28665981/ha117-endows-hl60-cells-with-a-stem-like-signature-by-inhibiting-the-degradation-of-dnmt1-via-its-ability-to-down-regulate-expression-of-the-ggl-domain-of-rgs6
#19
Shuangshuang Li, Xianqing Jin, Huan Wu, Yi Wang, Xiaoqing Li, Yuxia Guo, Shaoyan Liang
All-trans retinoic acid (ATRA) induces complete remission in almost all patients with acute promyelocytic leukemia (APL) via its ability to induce the in vivo differentiation of APL blasts. However, prolonged ATRA treatment can result in drug resistance. In previous studies, we generated a multi-drug-resistant HL60/ATRA cell line and found it to contain a new drug resistance-related gene segment, HA117. In this study, we demonstrate that ATRA induces multi-drug-resistant subpopulations of HL60 cells with a putative stem-like signature by up-regulating the expression of the new gene segment HA117...
2017: PloS One
https://www.readbyqxmd.com/read/28662299/thrombotic-risk-stratification-by-platelet-count-in-patients-with-antiphospholipid-antibodies-a-longitudinal-study
#20
Ryo Hisada, Masaru Kato, Eri Sugawara, Yuichiro Fujieda, Kenji Oku, Toshiyuki Bohgaki, Olga Amengual, Shinsuke Yasuda, Tatsuya Atsumi
BACKGROUND: Thrombocytopenia is a non-criteria clinical manifestation of antiphospholipid syndrome (APS). However, it remains to be elucidated whether thrombocytopenia increases thrombotic risk in antiphospholipid antibody (aPL) carriers. OBJECTIVES: To investigate the impact of platelet count in terms of predicting thrombotic events in aPL carriers and to stratify the thrombotic risk by combining platelet count and antiphospholipid score (aPL-S), which represents a quantification of aPL varieties and titres PATIENTS/METHODS: A single centre retrospective, longitudinal study comprising 953 consecutive patients who were suspected to have autoimmune disease between January 2002 and December 2006...
June 29, 2017: Journal of Thrombosis and Haemostasis: JTH
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