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https://www.readbyqxmd.com/read/27903985/the-tissue-inhibitor-of-metalloproteinases-1-timp-1-promotes-survival-and-migration-of-acute-myeloid-leukemia-cells-through-cd63-pi3k-akt-p21-signaling
#1
Dorian Forte, Valentina Salvestrini, Giulia Corradi, Lara Rossi, Lucia Catani, Roberto M Lemoli, Michele Cavo, Antonio Curti
We and others have shown that the Tissue Inhibitor of Metalloproteinases-1 (TIMP-1), a member of the inflammatory network exerting pleiotropic effects in the bone marrow (BM) microenvironment, regulates the survival and proliferation of different cell types, including normal hematopoietic progenitor cells. Moreover, TIMP-1 has been shown to be involved in cancer progression. However, its role in leukemic microenvironment has not been addressed. Here, we investigated the activity of TIMP-1 on Acute Myelogenous Leukemia (AML) cell functions...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27899805/circulating-tumour-dna-analysis-demonstrates-spatial-mutational-heterogeneity-that-coincides-with-disease-relapse-in-myeloma
#2
S Mithraprabhu, T Khong, M Ramachandran, A Chow, D Klarica, L Mai, S Walsh, D Broemeling, A Marziali, M Wiggin, J Hocking, A Kalff, B Durie, A Spencer
Mutational characterisation in multiple myeloma (MM) currently relies on bone marrow (BM) biopsy, which fails to capture the putative spatial and genetic heterogeneity of this multi-focal disease. Analysis of plasma (PL)-derived circulating free tumour DNA (ctDNA) as an adjunct to BM biopsy, for mutational characterisation and tracking disease progression, was evaluated. Paired BM MM cell DNA and ctDNA from 33 relapsed [RR] and 15 newly diagnosed [ND] patients were analysed for KRAS, NRAS, BRAF and TP53 mutations using the OnTarget™ Mutation Detection (OMD) platform...
November 30, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27899526/dynamic-pre-bcr-homodimers-fine-tune-autonomous-survival-signals-in-b-cell-precursor-acute-lymphoblastic-leukemia
#3
M Frank Erasmus, Ksenia Matlawska-Wasowska, Ichiko Kinjyo, Avanika Mahajan, Stuart S Winter, Li Xu, Michael Horowitz, Diane S Lidke, Bridget S Wilson
The pre-B cell receptor (pre-BCR) is an immature form of the BCR critical for early B lymphocyte development. It is composed of the membrane-bound immunoglobulin (Ig) heavy chain, surrogate light chain components, and the signaling subunits Igα and Igβ. We developed monovalent quantum dot (QD)-labeled probes specific for Igβ to study the behavior of pre-BCRs engaged in autonomous, ligand-independent signaling in live B cells. Single-particle tracking revealed that QD-labeled pre-BCRs engaged in transient, but frequent, homotypic interactions...
November 29, 2016: Science Signaling
https://www.readbyqxmd.com/read/27891534/graphene-oxide-nanosheets-stimulate-ruffling-and-shedding-of-mammalian-cell-plasma-membranes
#4
Chao Sun, Devin L Wakefield, Yimo Han, David A Muller, David A Holowka, Barbara A Baird, William R Dichtel
Graphene oxide (GO) has attracted intense interest for use in living systems and environmental applications. GO's compatibility with mammalian cells is sometimes inferred from its low cytotoxicity, but such conclusions ignore non-lethal effects that will influence GO's utility. Here we demonstrate, with rat basophilic leukemia (RBL) cells, profound plasma membrane (PM) ruffling and shedding induced by GO using confocal and live cell fluorescence microscopy, as well as scanning electron microscopy. These membrane structures contain immunoglobulin E receptors, are resistant to detergents, and lack detectable fluorescence labeling of F-actin and fibronectin...
August 11, 2016: Chem
https://www.readbyqxmd.com/read/27881873/induction-of-iron-excess-restricts-malignant-plasma-cells-expansion-and-potentiates-bortezomib-effect-in-models-of-multiple-myeloma
#5
J Bordini, S Galvan, M Ponzoni, M T S Bertilaccio, M Chesi, P L Bergsagel, C Camaschella, A Campanella
Leukemia accepted article preview online, 24 November 2016. doi:10.1038/leu.2016.346.
November 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27875673/recent-advances-in-engineered-t-cell-therapies-targeting-b-cell-malignancies
#6
Nathan Singh
Immunotherapy using engineered autologous T cells has been attempted for decades, but clinical trials have only recently demonstrated efficacy. The combination of enhanced manufacturing techniques, highly efficient engineering, appropriate target selection and synthetic receptors with potent T cell activating domains has led to the development of highly-active cellular therapy products. B-cell malignancies have served as the paradigmatic diseases to initially evaluate and subsequently hone engineered T cells targeting cancer...
October 2016: Discovery Medicine
https://www.readbyqxmd.com/read/27870947/subcellular-localization-of-the-flt3-itd-oncogene-plays-a-significant-role-in-the-production-of-nox-and-p22-phox-derived-reactive-oxygen-species-in-acute-myeloid-leukemia
#7
Jennifer N Moloney, Joanna Stanicka, Thomas G Cotter
Internal tandem duplication of the juxtamembrane domain of FMS-like tyrosine kinase 3 (FLT3-ITD) receptor is the most prevalent FLT3 mutation accounting for 20% of acute myeloid leukemia (AML) patients. FLT3-ITD mutation results in ligand-independent constitutive activation of the receptor at the plasma membrane and 'impaired trafficking' of the receptor in compartments of the endomembrane system, such as the endoplasmic reticulum (ER). FLT3-ITD expressing cells have been shown to generate increased levels of reactive oxygen species (ROS), in particular NADPH oxidase (NOX)-generated ROS which act as pro-survival signals...
November 11, 2016: Leukemia Research
https://www.readbyqxmd.com/read/27863543/reduced-humoral-immunity-and-atypical-cell-mediated-immunity-in-response-to-vaccination-in-cows-naturally-infected-with-bovine-leukemia-virus
#8
Meredith C Frie, Kelly R Sporer, Joseph C Wallace, Roger K Maes, Lorraine M Sordillo, Paul C Bartlett, Paul M Coussens
Bovine leukemia virus (BLV) is a retrovirus that is widely distributed across US dairy herds: over 83% of herds are BLV-infected and within-herd infection rates can approach 50%. BLV infection reduces both animal longevity and milk production and can interfere with normal immune health. With such a high prevalence of BLV infection in dairy herds, it is essential to understand the circumstances by which BLV negatively affects the immune system of infected cattle. To address this question, BLV- and BLV+ adult, lactating Holstein dairy cows were vaccinated with Bovi-Shield GOLD(®) FP(®) 5 L5 HB and their immune response to vaccination was measured over the course of 28days...
December 2016: Veterinary Immunology and Immunopathology
https://www.readbyqxmd.com/read/27862208/the-cytokines-and-cellular-responses-to-human-herpesvirus-6b-in-patients-with-b-acute-lymphoblastic-leukemia
#9
Faten Nefzi, Claude Lambert, Agnès Gautheret-Dejean, Sylvain Fisson, Quentin Khebizi, Abderrahim Khelif, Henri Agut, Mahjoub Aouni
Human herpesvirus-6 (HHV-6) is a β-herpesvirus with primary infection followed by its lifelong persistence in its host. The T-cell responses to HHV-6 mostly have been characterized using peripheral blood from healthy adults. Although the role of HHV-6 infection in immune modulation in some of the diseases was not elucidated. Therefore, we analyzed the immune response to HHV-6 infection in B-acute lymphobastic leukemia (B-ALL) patients. HHV-6 load was quantified in blood samples at the time of diagnosis of leukemia and at remission...
November 15, 2016: Microbiology and Immunology
https://www.readbyqxmd.com/read/27859216/cooperation-of-mll-af10-om-lz-with-ptpn11-activating-mutation-induced-monocytic-leukemia-with-a-shorter-latency-in-a-mouse-bone-marrow-transplantation-model
#10
Jen-Fen Fu, Sung-Tzu Liang, Ying-Jung Huang, Kung-Hao Liang, Tzung-Hai Yen, Der-Cherng Liang, Lee-Yung Shih
PTPN11 mutation, a RAS signaling pathway mutation, is associated with MLL translocations in acute leukemia. A girl with MLL/AF10 AML was found to carry PTPN11(G503A) . To study the impact of PTPN11 (G503A) cooperating with MLL/AF10 on leukemogenesis, we established a retroviral transduction/transplantation mouse model. Compared with the MLL/AF10(OM-LZ) leukemia cells harboring PTPN11 (wt) , the cells harboring PTPN11(G503A) were hypersensitive to GM-CSF and IL3, and more resistant to death upon treatment with daunorubicin but sensitive to cytarabine...
November 14, 2016: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/27859015/hla-e-allelic-genotype-correlates-with-hla-e-plasma-levels-and-predicts-early-progression-in-chronic-lymphocytic-leukemia
#11
Bettina Wagner, Fabiola da Silva Nardi, Sabine Schramm, Thomas Kraemer, Alexander A Celik, Jan Dürig, Peter A Horn, Ulrich Dührsen, Holger Nückel, Vera Rebmann
BACKGROUND: Human leukocyte antigen-E (HLA-E) is a nonclassical major histocompatibility complex class I molecule that recently came into sharper focus as a putative marker of advanced tumor stages and disease progression. In solid tumors, increased HLA-E expression as well as elevated soluble HLA-E (sHLA-E) plasma levels are associated with a poor prognosis; however, a role for HLA-E in hematologic malignancies remains to be established. METHODS: The authors analyzed HLA-E alleles and sHLA-E levels in a cohort of 110 individuals with chronic lymphocytic leukemia (CLL)...
November 2, 2016: Cancer
https://www.readbyqxmd.com/read/27853634/dynamic-alterations-of-bone-marrow-cytokine-landscape-of-myelodysplastic-syndromes-patients-treated-with-5-azacytidine
#12
Alena Moudra, Sona Hubackova, Veronika Machalova, Marketa Vancurova, Jiri Bartek, Milan Reinis, Zdenek Hodny, Anna Jonasova
Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal stem cell disorders characterized by ineffective hematopoiesis frequently progressing into acute myeloid leukemia (AML), with emerging evidence implicating aberrant bone marrow (BM) microenvironment and inflammation-related changes. 5-azacytidine (5-AC) represents standard MDS treatment. Besides inhibiting DNA/RNA methylation, 5-AC has been shown to induce DNA damage and apoptosis in vitro. To provide insights into in vivo effects, we assessed the proinflammatory cytokines alterations during MDS progression, cytokine changes after 5-AC, and contribution of inflammatory comorbidities to the cytokine changes in MDS patients...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27833979/multiple-myeloma-and-secondary-plasma-cell-leukemia
#13
Vitorino Modesto Dos Santos, Sandro Pinheiro Melim, Priscilla Souza de Faria, Viviane Vieira Passini, Mayza Lemes Duarte, Renata Athayde Casasanta
Plasma cell leukemia is very rare condition characterized by malignant proliferation of plasma cells in blood and bone marrow, which is aggressive and has a short survival even with conventional treatment. This ominous entity may be primary, or develops secondarily during the course of multiple myeloma. A 53-year-old Brazilian woman with multiple myeloma is described with bone marrow evaluation revealing 25% plasma cells. The quantification of plasma cell infiltration in bone marrow aspirate and immunohistochemistry study revealed consistent features of myeloma and plasma cell leukemia, and lambda light chain expression...
2016: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/27832383/use-of-acetaminophen-in-relation-to-the-occurrence-of-cancer-a-review-of-epidemiologic-studies
#14
REVIEW
Noel S Weiss
Acetaminophen has several pharmacologic properties that suggest it could be carcinogenic in human beings. A number of epidemiologic studies have been conducted to examine whether use of acetaminophen actually predisposes to the occurrence of one or more forms of cancer. There are inherent limitations to many of these studies, including the inaccurate identification of users and nonusers of acetaminophen, relatively short follow-up for cancer incidence, and the potential for confounding by indication. The present manuscript reviews the results of epidemiologic studies of acetaminophen use in relation to cancer incidence published through the end of 2015...
December 2016: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/27825464/prognostic-factors-and-indications-for-treatment-of-waldenstr%C3%A3-m-s-macroglobulinemia
#15
REVIEW
Robert A Kyle, Stephen M Ansell, Prashant Kapoor
Waldenström's Macroglobulinemia (WM) is characterized by the presence of an IgM monoclonal protein regardless of its size, 10% or more bone marrow infiltration by small lymphocytes with a plasmacytoid or plasma cell differentiation. These cells usually have the following markers: IgM+, CD5(-), CD10(-), CD19(+), CD20(+) and CD23(-). Chronic lymphocytic leukemia as well as other lymphoproliferative disorders such as mantle cell, marginal zone and mucosa-associated lymphoid tissue (MALT) lymphoma must be excluded...
June 2016: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/27824644/rapid-fatal-acute-peripheral-t-cell-lymphoma-associated-with-igg-plasma-cell-leukemia-and-iga-hypergammaglobulinemia
#16
Nives Jonjić, Irena Seili Bekafigo, Dora Fučkar Čupić, Ksenija Lučin, Antica Duletić Načinović, Toni Valković
Simultaneous occurrence of T-cell and B-cell neoplasms is rare, and etiologic relationships between these 2 malignancies are poorly understood. We describe the case of a 66-year-old woman who was admitted to the hospital because of fever, hemoptysis, lymphadenopathy, and skin rash. Enlarged lymph nodes in axillary, pectoral, paratracheal, and periportal regions as well as slight hepatomegaly and splenomegaly were confirmed. A peripheral blood smear revealed rouleaux formation and numerous circulating plasma cells, with plasmacytoid lymphocytes...
November 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/27822103/the-danish-national-multiple-myeloma-registry
#17
REVIEW
Peter Gimsing, Morten O Holmström, Tobias Wirenfelt Klausen, Niels Frost Andersen, Henrik Gregersen, Robert Schou Pedersen, Torben Plesner, Per Trøllund Pedersen, Mikael Frederiksen, Ulf Frølund, Carsten Helleberg, Annette Vangsted, Peter de Nully Brown, Niels Abildgaard
AIM: The Danish National Multiple Myeloma Registry (DMMR) is a population-based clinical quality database established in January 2005. The primary aim of the database is to ensure that diagnosis and treatment of plasma cell dyscrasia are of uniform quality throughout the country. Another aim is to support research. Patients are registered with their unique Danish personal identification number, and the combined use of DMMR, other Danish National registries, and the Danish National Cancer Biobank offers a unique platform for population-based translational research...
2016: Clinical Epidemiology
https://www.readbyqxmd.com/read/27819179/plasma-cell-leukemia-update-on-biology-and-therapy
#18
Roberto Mina, Mattia D'Agostino, Chiara Cerrato, Francesca Gay, Antonio Palumbo
Plasma cell leukemia (PCL) is a rare, but very aggressive, plasma cell dyscrasia, representing a distinct clinicopathological entity as compared to multiple myeloma (MM), with peculiar biological and clinical features. A hundred times rarer than MM, the disease course is characterized by short remissions and poor survival. PCL is defined by an increased percentage (>20%) and absolute number (>2 × 10(9)/l) of plasma cells in the peripheral blood. PCL is defined as 'primary' when peripheral plasmacytosis is detected at diagnosis, 'secondary' when leukemization occurs in a patient with preexisting MM...
November 6, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27816533/about-the-discrete-continuous-nature-of-a-hematopoiesis-model-for-chronic-myeloid-leukemia
#19
Marcos E Gaudiano, Tom Lenaerts, Jorge M Pacheco
Blood of mammals is composed of a variety of cells suspended in a fluid medium known as plasma. Hematopoiesis is the biological process of birth, replication and differentiation of blood cells. Despite of being essentially a stochastic phenomenon followed by a huge number of discrete entities, blood formation has naturally an associated continuous dynamics, because the cellular populations can - on average - easily be described by (e.g.) differential equations. This deterministic dynamics by no means contemplates some important stochastic aspects related to abnormal hematopoiesis, that are especially significant for studying certain blood cancer deceases...
December 2016: Mathematical Biosciences
https://www.readbyqxmd.com/read/27810077/chronic-myelogenous-leukemia-with-acquired-t-11-14-q13-q32-ccnd1-igh-a-case-report-and-literature-review
#20
M T Manda-Mapalo, P Khalili, D Quintana, I Rabinowitz, Q Y Zhang
Approximately 5-10% of chronic myeloid leukemia (CML) patients are found to have structural or numerical additional chromosomal abnormality (ACAs) in addition to the characteristic t(9;22)(q34;q11.2) BCR/ABL1 at the time of diagnosis. The prognostic significance of such additional chromosomal abnormalities has been controversial. Translocation t(11;14)(q13;q32) CCND1-IGH is typically associated with mantle cell lymphoma or a subset of plasma cell myeloma and is exceedingly rare in myeloid neoplasm. Here we report a unique case describing a patient found at diagnosis of chronic phase CML to have both the Philadelphia chromosome as well as t(11;14)-a rare cytogenetic combination...
October 2016: Cancer Genetics
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