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Treatment Plasma cell leukemia

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https://www.readbyqxmd.com/read/28423727/paclitaxel-synergizes-with-exposure-time-adjusted-cd22-targeting-immunotoxins-against-b-cell-malignancies
#1
Fabian Müller, Stephanie Stookey, Tyler Cunningham, Ira Pastan
CD22-targeted recombinant immunotoxins (rIT) are active in hairy cell leukemia or acute lymphoblastic leukemia (ALL), but not in mantle cell lymphoma (MCL) patients. The goal was to enhance rIT efficacy in vivo and to define a strong combination treatment. Activity of Moxetumomab pasudotox (Moxe) and LR combined with paclitaxel was tested against MCL cell lines in vitro and as bolus doses or continuous infusion in xenograft models. In the KOPN-8 ALL xenograft, Moxe or paclitaxel alone was active, but all mice died from leukemia; when combined, 60% of the mice achieved a sustained complete remission...
March 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28418845/preclinical-development-of-g1t38-a-novel-potent-and-selective-inhibitor-of-cyclin-dependent-kinases-4-6-for-use-as-an-oral-antineoplastic-in-patients-with-cdk4-6-sensitive-tumors
#2
John E Bisi, Jessica A Sorrentino, Jamie L Jordan, David D Darr, Patrick J Roberts, Francis X Tavares, Jay C Strum
Inhibition of the p16INK4a/cyclin D/CDK4/6/RB pathway is an effective therapeutic strategy for the treatment of estrogen receptor positive (ER+) breast cancer. Although efficacious, current treatment regimens require a dosing holiday due to severe neutropenia potentially leading to an increased risk of infections, as well as tumor regrowth and emergence of drug resistance. Therefore, a next generation CDK4/6 inhibitor that can inhibit proliferation of CDK4/6-dependent tumors while minimizing neutropenia could reduce both the need for treatment holidays and the risk of inducing drug resistance...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28404854/autologous-stem-cell-transplantation-disrupts-adaptive-immune-responses-during-rebound-shiv-viremia
#3
Daniel B Reeves, Christopher W Peterson, Hans-Peter Kiem, Joshua T Schiffer
Primary HIV-1 infection induces a virus-specific adaptive/cytolytic immune response that impacts plasma viral load setpoint and rate of progression to AIDS. Combination antiretroviral therapy (cART) suppresses plasma viremia to undetectable levels that rebound upon cART treatment interruption. Following cART withdrawal, the memory component of the virus-specific adaptive immune response may improve viral control compared to primary infection. Here, using primary infection and treatment interruption data from macaques infected with simian/human immunodeficiency virus (SHIV), we observe lower peak viral load but unchanged viral setpoint during viral rebound...
April 12, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28403213/m-copa-suppresses-endolysosomal-kit-akt-oncogenic-signalling-through-inhibiting-the-secretory-pathway-in-neoplastic-mast-cells
#4
Yasushi Hara, Yuuki Obata, Keita Horikawa, Yasutaka Tasaki, Kyohei Suzuki, Takatsugu Murata, Isamu Shiina, Ryo Abe
Gain-of-function mutations in Kit receptor tyrosine kinase result in the development of a variety of cancers, such as mast cell tumours, gastrointestinal stromal tumours (GISTs), acute myeloid leukemia, and melanomas. The drug imatinib, a selective inhibitor of Kit, is used for treatment of mutant Kit-positive cancers. However, mutations in the Kit kinase domain, which are frequently found in neoplastic mast cells, confer an imatinib resistance, and cancers expressing the mutants can proliferate in the presence of imatinib...
2017: PloS One
https://www.readbyqxmd.com/read/28337541/tyrosine-kinase-inhibitor-therapy-induced-changes-in-humoral-immunity-in-patients-with-chronic-myeloid-leukemia
#5
Hanna L M Rajala, Mohamed El Missiry, Anniina Ruusila, Perttu Koskenvesa, Tim H Brümmendorf, Bjorn T Gjertsen, Jeroen Janssen, Kourosh Lotfi, Berit Markevärn, Ulla Olsson-Strömberg, Leif Stenke, Jesper Stentoft, Johan Richter, Henrik Hjorth-Hansen, Anna Kreutzman, Satu Mustjoki
PURPOSE: Tyrosine kinase inhibitors (TKIs) have well-characterized immunomodulatory effects on T and NK cells, but the effects on the humoral immunity are less well known. In this project, we studied TKI-induced changes in B cell-mediated immunity. METHODS: We collected peripheral blood (PB) and bone marrow (BM) samples from chronic myeloid leukemia (CML) patients before and during first-line imatinib (n = 20), dasatinib (n = 16), nilotinib (n = 8), and bosutinib (n = 12) treatment...
March 23, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/28325251/interferon-induced-thrombotic-microangiopathy-tma-analysis-and-concise-review
#6
REVIEW
Ajay Kundra, Jen Chin Wang
Interferon (IFN) has been associated with development of thrombotic microangiopathy including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). We reviewed literature from the earliest reported association in 1993, to July 2016 and found 68 cases. Analysis of this data shows: (1) Mean age at diagnosis was 47 years (95% CI, 44-50). (2) Majority of cases were seen where IFN was used for the treatment of chronic myelogenous leukemia (CML), multiple sclerosis (MS), chronic hepatitis C virus infection (HCV) and one case each for hairy cell leukemia (HCL) and Sezary syndrome...
April 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28321034/galectin-9-as-a-predictive-marker-for-the-onset-of-immune-related-adverse-effects-associated-with-anti-ccr4-moab-therapy-in-patients-with-adult-t-cell-leukemia
#7
Tareg Omer Mohammed, Haorile Chagan-Yasutan, Yugo Ashino, Wakana Nakayama, Yayoi Takahashi, Taizo Shimomura, Tetsuhiro Fujimoto, Yuko Watanabe, Toshiro Niki, Hitoshi Suzushima, Toshio Hattori
Adult T-cell leukemia/lymphoma (ATL/ATLL) is one of the most malignant lymphomas with poor prognosis. ATL/ATLL cells express CC chemokine receptor 4, and mogamulizumab (anti-CCR4 monoclonal antibody) exhibits strong cytotoxicity for ATL/ATLL cells. We analyzed plasma samples of 6 patients with ATL/ATLL treated with chemotherapy followed by mogamulizumab therapy (mogatherapy) for changes in the levels of biomarkers in relation to immune-related adverse effects. As treatment is often associated with skin eruptions, we investigated the profiles of inflammatory cytokines, including galectin-9 (Gal-9), which becomes increased in various infectious diseases and allergic patients...
March 2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28303902/ms4a4a-a-novel-cell-surface-marker-for-m2-macrophages-and-plasma-cells
#8
Ratna Sanyal, Maria J Polyak, Jonathan Zuccolo, Mandip Puri, Lili Deng, Luc Roberts, Ania Zuba, Jan Storek, Joanne M Luider, Ellen M Sundberg, Adnan Mansoor, Eva Baigorri, Michael P Chu, Andrew R Belch, Linda M Pilarski, Julie P Deans
MS4A4A is a member of the membrane-spanning, 4 domain family, subfamily A (MS4A) that includes CD20 (MS4A1), FcRβ (MS4A2) and Htm4 (MS4A3). Like the first three members of this family, transcription of MS4A4A appears to be limited to hematopoietic cells. To evaluate expression of the MS4A4A protein in hematopoietic cell lineages and subsets we generated monoclonal antibodies against extracellular epitopes for use in flow cytometry. In human peripheral blood we found that MS4A4A is expressed at the plasma membrane in monocytes but not in granulocytes or lymphocytes...
March 17, 2017: Immunology and Cell Biology
https://www.readbyqxmd.com/read/28288853/establishing-evidence-based-thresholds-and-laboratory-practices-to-reduce-inappropriate-treatment-of-pseudohyperkalemia
#9
Pratistha Ranjitkar, Dina N Greene, Geoffrey S Baird, Andrew N Hoofnagle, Patrick C Mathias
BACKGROUND: Unrecognized pseudohyperkalemia (PHK), defined as an artificial increase in measured potassium concentration, due to thrombocytosis and leukocytosis can lead to inappropriate patient treatment. Understanding the laboratory and patient characteristics that increase risk of PHK is key to preventing diagnostic errors. METHODS: Serum/plasma potassium results collected at 2 laboratories over 4years were selected based on blood cell counts collected within 24h and whole blood potassium concentrations determined within 2h of the serum/plasma sample...
March 10, 2017: Clinical Biochemistry
https://www.readbyqxmd.com/read/28283735/in-vitro-and-in-vivo-evaluation-of-dasatinib-and-imatinib-on-physiological-parameters-of-pulmonary-arterial-hypertension
#10
Bethany Baumgart, Mausumee Guha, James Hennan, Julia Li, Jochen Woicke, Damir Simic, Michael Graziano, Nicola Wallis, Thomas Sanderson, Roderick Todd Bunch
PURPOSE: Pulmonary arterial hypertension (PAH) results from occlusion or vasoconstriction of pulmonary vessels, leading to progressive right ventricular failure. Dasatinib, a BCR-ABL1 tyrosine kinase inhibitor (TKI) approved for the treatment of chronic myelogenous leukemia, has been associated with PAH. In contrast, the BCR-ABL1 TKI imatinib has demonstrated anti-vasoproliferative properties and has been investigated as a potential treatment for PAH. Here we describe studies evaluating the effects of dasatinib and imatinib on cardiovascular and pulmonary functions to understand the reported differential consequences of the two TKIs in a clinical setting...
March 10, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28270565/midostaurin-a-novel-protein-kinase-inhibitor-for-the-treatment-of-acute-myelogenous-leukemia-insights-from-human-absorption-metabolism-and-excretion-studies-of-a-bddcs-ii-drug
#11
Handan He, Phi Tran, Helen Gu, Vivienne Tedesco, Jin Zhang, Wen Lin, Ewa Gatlik, Kai Klein, Tycho Heimbach
The absorption, metabolism, and excretion of midostaurin, a potent class III tyrosine protein kinase inhibitor for acute myelogenous leukemia, were evaluated in healthy subjects. A microemulsion formulation was chosen to optimize absorption. After a 50-mg [(14)C]midostaurin dose, oral absorption was high (>90%) and relatively rapid. In plasma, the major circulating components were midostaurin (22%), CGP52421 (32.7%), and CGP62221 (27.7%). Long plasma half-lives were observed for midostaurin (20.3 hours), CGP52421 (495 hours), and CGP62221 (33...
May 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28240053/plasma-matrix-metalloprotease-9-correlates-with-blood-lymphocytosis-leukemic-cell-invasiveness-and-prognosis-in-b-cell-chronic-lymphocytic-leukemia
#12
Milena Gusella, Caterina Bolzonella, Rossella Paolini, Elisabetta Rodella, Laura Bertolaso, Cinzia Scipioni, Silvia Bellini, Antonio Cuneo, Felice Pasini, Emilio Ramazzina
The complex biology underlying chronic lymphocytic leukemia cell migration and tissue invasiveness is not yet completely understood and might provide novel predictive markers and therapeutic targets. A total of 36 patients out of treatment from at least 3 months were enrolled and followed up for a median period of 44.2 months (range: 4.4-99.2). Matrix metalloprotease 9 and tissue inhibitor of metalloproteases 1 plasma levels and production/release from lymphoid cells were measured by zymography and enzyme-linked immunosorbent assay (ELISA) analysis...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28186131/recq1-helicase-is-involved-in-replication-stress-survival-and-drug-resistance-in-multiple-myeloma
#13
E Viziteu, B Klein, J Basbous, Y-L Lin, C Hirtz, C Gourzones, L Tiers, A Bruyer, L Vincent, C Grandmougin, A Seckinger, H Goldschmidt, A Constantinou, P Pasero, D Hose, J Moreaux
Multiple myeloma (MM) is a plasma cell cancer with poor survival, characterized by the expansion of multiple myeloma cells (MMCs) in the bone marrow. Using a microarray-based genome-wide screen for genes responding to DNA methyltransferases (DNMT) inhibition in MM cells, we identified RECQ1 among the most downregulated genes. RecQ helicases are DNA unwinding enzymes involved in the maintenance of chromosome stability. Here, we show that RECQ1 is significantly overexpressed in MMCs compared to normal plasma cells and that increased RECQ1 expression is associated with poor prognosis in three independent cohorts of patients...
February 10, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28179997/the-plant-defensin-nad1-induces-tumor-cell-death-via-a-non-apoptotic-membranolytic-process
#14
Amy A Baxter, Ivan Kh Poon, Mark D Hulett
Cationic anti-microbial peptides (CAPs) have an important role in host innate defense against pathogens such as bacteria and fungi. Many CAPs including defensins also exhibit selective cytotoxic activity towards mammalian cells via both apoptotic and non-apoptotic processes, and are being investigated as potential anticancer agents. The anti-fungal plant defensin from ornamental tobacco, Nicotiana alata Defensin 1 (NaD1), was recently shown to induce necrotic-like cell death in a number of tumor cell types within 30 min of treatment, at a concentration of 10 μM...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28159900/serum-mir-29a-is-upregulated-in-acute-graft-versus-host-disease-and-activates-dendritic-cells-through-tlr-binding
#15
Parvathi Ranganathan, Apollinaire Ngankeu, Nina C Zitzer, PierPaolo Leoncini, Xueyan Yu, Lucia Casadei, Kishore Challagundla, Dawn K Reichenbach, Sabrina Garman, Amy S Ruppert, Stefano Volinia, Jessica Hofstetter, Yvonne A Efebera, Steven M Devine, Bruce R Blazar, Muller Fabbri, Ramiro Garzon
Acute graft-versus-host disease (aGVHD) continues to be a frequent and devastating complication of allogeneic hematopoietic stem cell transplantation (HSCT), posing as a significant barrier against the widespread use of HSCTs as a curative modality. Recent studies suggested serum/plasma microRNAs (miRs) may predict aGVHD onset. However, little is known about the functional role of circulating miRs in aGVHD. In this article, we show in two independent cohorts that miR-29a expression is significantly upregulated in the serum of allogeneic HSCT patients at aGVHD onset compared with non-aGVHD patients...
March 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28151428/bone-marrow-microenvironment-derived-signals-induce-mcl-1-dependence-in-multiple-myeloma
#16
Vikas A Gupta, Shannon M Matulis, Jason E Conage-Pough, Ajay K Nooka, Jonathan L Kaufman, Sagar Lonial, Lawrence H Boise
Multiple myeloma is highly dependent on the bone marrow microenvironment until progressing to very advanced extramedullary stages of the disease such as plasma cell leukemia. Stromal cells in the bone marrow secrete a variety of cytokines that promote plasma cell survival by regulating antiapoptotic members of the Bcl-2 family including Mcl-1, Bcl-xL, and Bcl-2. Although the antiapoptotic protein on which a cell depends is typically consistent among normal cells of a particular phenotype, Bcl-2 family dependence is highly heterogeneous in multiple myeloma...
April 6, 2017: Blood
https://www.readbyqxmd.com/read/28122281/anti-cancer-effect-of-clofazimine-as-a-single-agent-and-in-combination-with-cisplatin-on-u266-multiple-myeloma-cell-line
#17
İpek Z Durusu, Hazal H Hüsnügil, Heval Ataş, Ayşenur Biber, Selin Gerekçi, Ezgi A Güleç, Can Özen
Multiple Myeloma (MM) is a malignant neoplasm of bone marrow plasma B cells with high morbidity. Clofazimine (CLF) is an FDA-approved leprostatic, anti-tuberculosis, and anti-inflammatory drug that was previously shown to have growth suppression effect on various cancer types such as hepatocellular, lung, cervix, esophageal, colon, and breast cancer as well as melanoma, neuroblastoma, and leukemia. The objective of this study was to evaluate the anticancer effect and mechanism of CLF on U266 MM cell line. CLF (10μM, 24h) treatment resulted up to 72% growth suppression on a panel of hematological cell lines...
January 16, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28061985/multiple-myeloma-epidemiology-and-survival-a-unique-malignancy
#18
REVIEW
Dickran Kazandjian
Multiple myeloma (MM), although a rare disease, is the second most common hematologic malignancy. It is found in the spectrum of plasma cell dyscrasias, which begins with monoclonal gammopathy of unknown significance (MGUS) to overt plasma cell leukemia and extramedullary myeloma. MM is associated with significant morbidity due to its end-organ destruction. It is a disease of the older population and its incidence in the African American population is twice that of the European American population. Improvements in the treatment of MM in the past couple of decades, beginning with the use of autologous stem cell transplantation followed by availability of novel treatments such as immunomodulatory drugs (ImIDs) and proteasome inhibitors (PIs) has transformed the natural history of the disease leading to longer survival times...
December 2016: Seminars in Oncology
https://www.readbyqxmd.com/read/28056193/reduced-cd62l-expression-on-t-cells-and-increased-soluble-cd62l-levels-predict-molecular-response-to-tyrosine-kinase-inhibitor-therapy-in-early-chronic-phase-chronic-myelogenous-leukemia
#19
Sieghart Sopper, Satu Mustjoki, Deborah White, Timothy Hughes, Peter Valent, Andreas Burchert, Bjørn T Gjertsen, Günther Gastl, Matthias Baldauf, Zlatko Trajanoski, Frank Giles, Andreas Hochhaus, Thomas Ernst, Thomas Schenk, Jeroen J W M Janssen, Gert J Ossenkoppele, Kimmo Porkka, Dominik Wolf
Purpose Immunologic surveillance of minimal residual disease in chronic myelogenous leukemia (CML) may be relevant for long-term control or cure of CML. Little is known about immune-modulatory effects of nilotinib in vivo, potentially predicting response to therapy. Patients and Methods A prospective and comprehensive flow cytometry-based immunomonitoring program paralleled the ENEST1st clinical study, investigating 52 nilotinib-naïve patients with chronic-phase CML. Data were verified in independent validation cohorts...
January 10, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28053193/promyelocytic-extracellular-chromatin-exacerbates-coagulation-and-fibrinolysis-in-acute-promyelocytic-leukemia
#20
Muhua Cao, Tao Li, Zhangxiu He, Lixiu Wang, Xiaoyan Yang, Yan Kou, Lili Zou, Xue Dong, Valerie A Novakovic, Yayan Bi, Junjie Kou, Bo Yu, Shaohong Fang, Jinghua Wang, Jin Zhou, Jialan Shi
Despite routine treatment of unselected acute promyelocytic leukemia (APL) with all-trans-retinoic acid (ATRA), early death due to hemorrhage remains unacceptably common and the mechanism underlying this complication remains elusive. We have recently demonstrated that APL cells undergo a novel cell death program, termed ETosis, which involves release of extracellular chromatin. However, the role of promyelocytic extracellular chromatin in APL-associated coagulation remains unclear. Our objectives were to identify the novel role of ATRA-promoted extracellular chromatin in inducing a hypercoagulable and hyperfibrinolytic state in APL and to evaluate its interaction with fibrin and endothelial cells (ECs)...
January 4, 2017: Blood
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