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https://read.qxmd.com/read/31101627/short-regimen-of-rituximab-plus-lenalidomide-in-follicular-lymphoma-patients-in-need-of-first-line-therapy
#1
Emanuele Zucca, Stephanie Rondeau, Anna Vanazzi, Bjorn Østenstad, Ulrich J M Mey, Daniel Rauch, Björn E Wahlin, Felicitas Hitz, Micaela Hernberg, Ann-Sofie Johansson, Peter de Nully Brown, Hans Hagberg, Andrés J M Ferreri, Andreas Lohri, Urban Novak, Thilo Zander, Hanne Bersvendsen, Mario Bargetzi, Walter Mingrone, Fatime Krasniqi, Stefan Dirnhofer, Stefanie Hayoz, Hanne Hawle, Simona Berardi Vilei, Michele Ghielmini, Eva Kimby
The SAKK 35/10 phase-2 trial (NCT01307605), developed by the Swiss Group for Clinical Cancer Research (SAKK) and the Nordic Lymphoma Group (NLG), compared the activity of rituximab versus rituximab plus lenalidomide in untreated follicular lymphoma patients in need of systemic therapy. Patients were randomized to rituximab (375 mg/m2 IV on day 1, weeks 1-4, repeated week 12-15 in responding patients) or to rituximab (same schedule) in combination with lenalidomide (15 mg PO daily for 18 weeks). Primary endpoint was complete response (CR/CRu) rate at 6 months...
May 17, 2019: Blood
https://read.qxmd.com/read/31101626/safety-of-car-t-cell-therapy-in-patients-with-b-cell-lymphoma-and-chronic-hepatitis-b-or-c-virus-infection
#2
Paolo Strati, Loretta J Nastoupil, Luis E Fayad, Felipe Samaniego, Sherry Adkins, Sattva S Neelapu
No abstract text is available yet for this article.
May 17, 2019: Blood
https://read.qxmd.com/read/31101625/identification-and-transcriptome-analysis-of-erythroblastic-island-macrophages
#3
Wei Li, Yaomei Wang, Huizhi Zhao, Huan Zhang, Yuanlin Xu, Shihui Wang, Xinhua Guo, Yumin Huang, Shijie Zhang, Yongshuai Han, Xianfang Wu, Charles M Rice, Gang Huang, Patrick G Gallagher, Avital Mendelson, Karina Yazdanbakhsh, Jing Liu, Lixiang Chen, Xiuli An
The erythroblastic island (EBI), composed of a central macrophage and surrounding erythroid cells, was the first hematopoietic niche discovered. The identity of EBI macrophages has thus far remained elusive. Given that Epo is essential for erythropoiesis and that Epor is expressed in numerous non-erythoid cells, we hypothesized that EBI macrophages express Epor so that Epo can act on both erythroid cells and EBI macrophages simultaneously to ensure efficient erythropoiesis. To test this notion, we employed Epor-eGFPcre knockin mouse model...
May 17, 2019: Blood
https://read.qxmd.com/read/31101624/cysteine-depletion-targets-leukemia-stem-cells-through-inhibition-of-electron-transport-complex-ii
#4
Courtney L Jones, Brett M Stevens, Angelo D'Alessandro, Rachel Culp-Hill, Julie A Reisz, Shanshan Pei, Annika Gustafson, Nabilah Khan, James DeGregori, Daniel A Pollyea, Craig T Jordan
We have previously demonstrated that oxidative phosphorylation is required for the survival of human leukemia stem cells (LSCs) from acute myeloid leukemia (AML) patients. More recently, we demonstrated that LSCs in de novo AML patients rely on amino acid metabolism to drive oxidative phosphorylation. Notably, while overall levels of amino acids contribute to LSC energy metabolism, our current findings suggest that cysteine may be of particular importance for LSC survival. We demonstrate that exogenous cysteine is metabolized exclusively to glutathione...
May 17, 2019: Blood
https://read.qxmd.com/read/31101623/plasmin-mediated-fibrinolysis-enables-macrophage-migration-in-a-murine-model-of-inflammation
#5
Lakmali Munasinghage Silva, Andrew Garry Lum, Collin Tran, Molly W Shaw, Zhen Gao, Matthew J Flick, Niki Moutsopoulos, Thomas H Bugge, Eric S Mullins
Efficient migration of macrophages to sites of inflammation requires cell surface-bound plasmin(ogen). Here, we investigated the mechanisms underlying the deficits of plasmin(ogen)- mediated macrophage migration in two models: murine thioglycollate-induced peritonitis and in vitro macrophage migration. As previously reported, macrophage migration into the peritoneal cavity of mice in response to thioglycollate was significantly impaired in the absence of plasminogen. Fibrin(ogen) deposition was noted in the peritoneal cavity in response to thioglycollate, with a significant increase in fibrin(ogen) in the plasminogen-deficient mice...
May 17, 2019: Blood
https://read.qxmd.com/read/31101622/recurrent-msc-e116k-mutations-in-alk-negative-anaplastic-large-cell-lymphoma
#6
Rebecca A Luchtel, Michael T Zimmermann, Guangzhen Hu, Surendra Dasari, Manli Jiang, Naoki Oishi, Hailey K Jacobs, Yu Zeng, Tanya Hundal, Karen L Rech, Rhett P Ketterling, Jeong-Heon Lee, Bruce W Eckloff, Huihuang Yan, Krutika S Gaonkar, Shulan Tian, Zhenqing Ye, Marshall E Kadin, Jagmohan Sidhu, Liuyan Jiang, Jesse Voss, Brian K Link, Sergei I Syrbu, Fabio Facchetti, N Nora Bennani, Susan L Slager, Tamas Ordog, Jean-Pierre Kocher, James R Cerhan, Steve Ansell, Andrew L Feldman
Anaplastic large cell lymphomas (ALCLs) represent a relatively common group of T-cell non-Hodgkin lymphomas (T-NHLs) that are unified by similar pathologic features but demonstrate marked genetic heterogeneity. ALCLs are broadly classified as being ALK-positive or ALK-negative, based on the presence or absence of ALK rearrangements. Exome sequencing of 62 T-NHLs identified a previously unreported recurrent mutation in the musculin gene, MSC E116K , exclusively in ALK-negative ALCLs. Additional sequencing for a total of 238 T-NHLs confirmed the specificity of MSC E116K for ALK-negative ALCL and further demonstrated that 14/15 mutated cases (93%) had co-existing DUSP22 rearrangements...
May 17, 2019: Blood
https://read.qxmd.com/read/31101621/targeting-glycogen-synthase-kinase-3-for-therapeutic-benefit-in-lymphoma
#7
Xiaosheng Wu, Mary Stenson, Jithma Abeykoon, Kevin Edward Nowakowski, Lianwen Zhang, Joshua Lawson, Linda Wellik, Ying Li, Jordan Krull, Kerstin Wenzl, Anne J Novak, Steve Ansell, Gail Bishop, Daniel D Billadeau, Kah Whye Peng, Francis Giles, Daniel M Schmitt, Thomas E Witzig
Targeting the B-cell receptor and PI3K/mTOR signaling pathways has shown meaningful but incomplete anti-tumor activity in lymphoma. Glycogen Synthase 3 (GSK3) kinase α and β are two homologous and functionally overlapping serine/threonine kinases that phosphorylate multiple protein substrates in several of key signaling pathways. To date, no agents targeting GSK3 have been approved for lymphoma therapy. We show that lymphoma cells abundantly express GSK3α and GSK3β compared to normal B- and T-lymphocytes at both mRNA and protein levels...
May 17, 2019: Blood
https://read.qxmd.com/read/31076448/chronic-lymphocytic-leukemia-cells-impair-mitochondrial-fitness-in-cd8-t-cells-and-impede-car-t-cell-efficacy
#8
Jaco A C van Bruggen, Anne W J Martens, Joseph A Fraietta, Tom Hofland, Sanne H Tonino, Eric Eldering, Mark-David Levin, Peter J Siska, Sanne Endstra, Jeffrey C Rathmell, Carl H June, David L Porter, J Joseph Melenhorst, Arnon P Kater, Gerritje J W van der Windt
Pharmacologic agents that modulate ubiquitin ligase activity to induce protein degradation are a major new class of therapeutic agents, active in a number of hematologic malignancies. However, we currently have a limited understanding of the determinants of activity of these agents and how resistance develops. We developed and utilized a novel quantitative, targeted mass spectrometry (MS) assay to determine the relative activities, kinetics, and cell-type specificity of thalidomide and four analogs, all but one of which are in clinical use or clinical trials for hematologic malignancies...
May 10, 2019: Blood
https://read.qxmd.com/read/31076447/spectrum-of-asxl1-mutations-in-primary-myelofibrosis-prognostic-impact-of-the-asxl1-p-g646wfs-12-mutation
#9
Giada Rotunno, Carmela Mannarelli, Giada Brogi, Annalisa Pacilli, Francesca Gesullo, Francesco Mannelli, Sara Fiaccabrino, Benedetta Sordi, Chiara Paoli, Ilaria Marone, Elisa Rumi, Rossella Manfredini, Giovanni Barosi, Mario Cazzola, Alessandro M Vannucchi, Paola Guglielmelli
No abstract text is available yet for this article.
May 10, 2019: Blood
https://read.qxmd.com/read/31076446/hepatic-leukemia-factor-is-a-novel-leukemic-stem-cell-regulator-in-dnmt3a-npm1-and-flt3-itd-triple-mutated-aml
#10
Swati Garg, Armando Reyes-Palomares, Lixiazi He, Anne Bergeron, Vincent-Philippe Lavallée, Sébastien Lemieux, Patrick Gendron, Christian Rohde, Jianglong Xia, Prarabdha Jagdhane, Carsten Müller-Tidow, Daniel B Lipka, Suzan Imren, R Keith Humphries, Claudia Waskow, Binje Vick, Irmela Jeremias, Guillaume Richard-Carpentier, Josée Hébert, Guy Sauvageau, Judith Zaugg, Frédéric Barabé, Caroline Pabst
FLT3, DNMT3A, and NPM1 are the most frequently mutated genes in cytogenetically normal acute myeloid leukemia (AML), but little is known about how these mutations synergize upon co-occurrence. Here we show that triple-mutated AML is characterized by high leukemia stem cell (LSC) frequency, an aberrant leukemia specific GPR56high CD34low immunophenotype, and synergistic upregulation of Hepatic Leukemia Factor (HLF). Cell sorting based on the LSC marker GPR56 allowed isolation of triple mutated from DNMT3A/NPM1 double-mutated subclones...
May 10, 2019: Blood
https://read.qxmd.com/read/31076445/cuplike-nuclear-morphology-is-highly-associated-with-ikzf1-deletion-in-pediatric-precursor-b-cell-all
#11
Weijie Li, Linda D Cooley, Keith August, Aida I Richardson, David L Zwick, Lei Shao, Atif Ahmed, Midhat S Farooqi
No abstract text is available yet for this article.
May 10, 2019: Blood
https://read.qxmd.com/read/31076444/-osteopontin-mediates-murine-transfusion-related-acute-lung-injury-via-stimulation-of-pulmonary-neutrophil-accumulation
#12
Rick Kapur, Gopinath Kasetty, Johan Rebetz, Arne Egesten, John W Semple
Transfusion-related acute lung injury (TRALI) is one of the leading causes of transfusionrelated fatalities and is characterized by the onset of acute respiratory distress within 6 hours upon blood transfusion. Specific therapies are unavailable. Pre-existing inflammation is a risk factor for TRALI and neutrophils (PMNs) are considered to be the major pathogenic cells. Osteopontin (OPN) is a multifunctional protein expressed at sites of inflammation and, for example, is involved in pulmonary disorders, can regulate cellular migration and can function as a PMN-chemoattractant...
May 10, 2019: Blood
https://read.qxmd.com/read/31076443/patrolling-monocytes-scavenge-endothelial-adherent-sickle-rbc-a-novel-mechanism-of-inhibition-of-vaso-occlusion-in-scd
#13
Yunfeng Liu, Hui Zhong, Weili Bao, Avital Mendelson, Xiuli An, Patricia Shi, Stella T Chou, Deepa Manwani, Karina Yazdanbakhsh
Painful vaso-occlusive crisis (VOC) is the most common complication of sickle cell disease (SCD). Increasing evidence suggests that vaso-occlusion is initiated by increased adherence of sickle red blood cells (RBC) to the vascular endothelium. Thus, the mechanisms that remove endothelial- attached sickle RBCs from the microvasculature are expected to be critical for optimal blood flow and prevention of VOC in SCD. We hypothesized that patrolling monocytes (PMo) which protect against vascular damage by scavenging cellular debris, could remove endothelial adherent sickle RBCs and ameliorate VOC in SCD...
May 10, 2019: Blood
https://read.qxmd.com/read/31076442/the-enhancer-rna-ariel-activates-the-oncogenic-transcriptional-program-in-t-cell-acute-lymphoblastic-leukemia
#14
Shi Hao Tan, Wei Zhong Leong, Phuong Cao Thi Ngoc, Tze King Tan, Fatima Carla Bertulfo, Mei Chee Lim, Omer An, Zhenhua Li, Allen Eng Juh Yeoh, Melissa J Fullwood, Daniel G Tenen, Takaomi Sanda
The oncogenic transcription factor TAL1 regulates the transcriptional program in T-cell acute lymphoblastic leukemia (T-ALL). ARID5B is one of critical downstream targets of TAL1 which further activates the oncogenic regulatory circuit in T-ALL cells. Here, we elucidated the molecular functions of the non-coding RNA, ARID5B Inducing Enhancer Associated Long non-coding RNA (ARIEL), in T-ALL pathogenesis. We demonstrated that ARIEL is specifically activated in TAL1-positive T-ALL cases, and its expression is associated with ARID5B enhancer activity...
May 10, 2019: Blood
https://read.qxmd.com/read/31076441/signaling-mechanisms-inducing-hypo-responsiveness-of-phagocytes-during-systemic-inflammation
#15
Nicole Freise, Alina Burghard, Theresa Ortkras, Niklas Daber, Achmet Imam Chasan, Saskia-L Jauch, Olesja Fehler, Julia Hillebrand, Mosab Schakaki, Jessica Rojas, Bodo Grimbacher, Thomas Vogl, Andreas Hoffmeier, Sven Martens, Johannes Roth, Judith Austermann
The inflammatory responsiveness of phagocytes to exogenous and endogenous stimuli is tightly regulated. This regulation plays an important role in systemic inflammatory response syndromes (SIRS). In SIRS phagocytes initially develop a hyper-inflammatory response followed by a secondary state of hypo-responsiveness, a so called tolerance. This hypo-responsiveness can be induced by endotoxin stimulation of Toll-like receptor 4 (TLR4) resulting in an ameliorated response after subsequent re-stimulation. This modification of inflammatory response patterns has been described as innate immune memory...
May 10, 2019: Blood
https://read.qxmd.com/read/31064751/mutational-landscape-of-the-transcriptome-offers-putative-targets-for-immunotherapy-of-myeloproliferative-neoplasms
#16
Fiorella Schischlik, Roland Jäger, Felix Rosebrock, Eva Hug, Michael K Schuster, Raimund Holly, Elisabeth Fuchs, Jelena D Milosevic Feenstra, Edith Bogner, Bettina Gisslinger, Martin Schalling, Elisa Rumi, Daniela Pietra, Gottfried F Fischer, Ingrid Faé, Loan Vulliard, Jörg Menche, Torsten Haferlach, Manja Meggendorfer, Anna Stengel, Christoph Bock, Mario Cazzola, Heinz Gisslinger, Robert Kralovics
Ph-negative myeloproliferative neoplasms (MPNs) are hematological cancers subdivided into entities with distinct clinical features. Somatic mutations in JAK2, CALR, and MPL have been described as drivers of the disease, together with a variable landscape of non-driver mutations. Despite detailed knowledge of disease mechanisms, targeted therapies effective enough to eliminate MPN cells are still missing. In this study, we aimed to comprehensively characterize in 113 MPN patients the mutational landscape of the granulocyte transcriptome using RNA-seq data and subsequently examine the applicability of immunotherapeutic strategies for MPN patients...
May 7, 2019: Blood
https://read.qxmd.com/read/31064750/hydroa-vacciniforme-like-lymphoproliferative-disorder-an-ebv-disease-with-a-low-risk-of-systemic-illness-in-caucasians
#17
Jeffrey I Cohen, Irini Manoli, Kennichi C Dowdell, Tammy A Krogmann, Deborah Tamura, Pierce Radecki, Wei Bu, Siu-Ping Turk, Kelly Liepshutz, Ronald L Hornung, Hiva Fassihi, Robert P Sarkany, Lori L Bonnycastle, Peter S Chines, Amy J Swift, Timothy G Myers, Melissa A Levoska, John J DiGiovanna, Francis S Collins, Kenneth H Kraemer, Stefania Pittaluga, Elaine S Jaffe
Patients with classic hydroa vacciniforme-like lymphoproliferative disorder (HVLPD) typically have high levels of Epstein-Barr virus (EBV) DNA in T cells and/or NK cells in blood, and skin lesions induced by sun exposure that are infiltrated with EBV-infected lymphocytes. HVLPD is very rare in the United States and Europe, but more common in Asia and South America. The disease can progress to a systemic form which may result in fatal lymphoma. We report our 11-year experience with 16 HVLPD patients from the United States and England and found that Caucasians were less likely to develop systemic EBV disease (1/10) than non-Caucasians (5/6)...
May 7, 2019: Blood
https://read.qxmd.com/read/31064749/diagnostic-high-throughput-sequencing-of-2-396-patients-with-bleeding-thrombotic-and-platelet-disorders
#18
Kate Downes, Karyn Megy, Daniel Duarte, Minka Vries, Johanna Gebhart, Stefanie Hofer, Olga Shamardina, Sri V V Deevi, Jonathan Stephens, Rutendo Mapeta, Salih Tuna, Namir Al Hasso, Martin W Besser, Nichola Cooper, Louise Daugherty, Nick Gleadall, Daniel Greene, Matthias Haimel, Howard Martin, Sofia Papadia, Shoshana Revel-Vilk, Suthesh Sivapalaratnam, Emily Symington, Will Thomas, Chantal Thys, Alexander Tolios, Christopher J Penkett, Willem H Ouwehand, Stephen Abbs, Michael A Laffan, Ernest Turro, Ilenia Simeoni, Andrew D Mumford, Yvonne M C Henskens, Ingrid Pabinger, Keith Gomez, Kathleen Freson
A targeted high-throughput sequencing (HTS) panel test for clinical diagnostics requires careful consideration of the inclusion of appropriate diagnostic-grade genes, the ability to detect multiple types of genomic variation with high levels of analytic sensitivity and reproducibility, and variant interpretation by a multi-disciplinary team (MDT) in the context of the clinical phenotype. We have sequenced 2,396 index patients using the ThromboGenomics HTS panel test of diagnostic-grade genes known to harbour variants associated with rare bleeding, thrombotic or platelet disorders (BTPD)...
May 7, 2019: Blood
https://read.qxmd.com/read/31043425/benefits-and-challenges-with-diagnosing-chronic-and-late-acute-gvhd-in-children-using-the-nih-consensus-criteria
#19
Geoffrey D E Cuvelier, Eneida R Nemecek, Justin T Wahlstrom, Carrie L Kitko, Victor Anthony Lewis, Tal Schechter, David A Jacobsohn, Andrew C Harris, Michael A Pulsipher, Henrique Bittencourt, Sung Won Choi, Emi H Caywood, Kimberly A Kasow, Monica Bhatia, Benjamin R Oshrine, Allyson Flower, Sonali Chaudhury, Donald Coulter, Joseph H Chewning, Michael Joyce, Süreyya Savaşan, Anna B Pawlowska, Gail C Megason, David Mitchell, Alexandra C Cheerva, Anita Lawitschka, Lori J West, Bo Pan, Yazid N Al-Hamarneh, Anat Halevy, Kirk R Schultz
Chronic graft-versus-host disease (cGvHD) and late-acute GvHD (L-aGvHD) are understudied complications of allogeneic hematopoietic stem cell transplantation in children. The National Institutes of Health Consensus Criteria (NIH-CC) were designed to improve the diagnostic accuracy of cGvHD and better classify GvHD syndromes but have not been validated in patients <18-years of age. The objectives of this prospective, multi-institution study were to determine: (1) if the NIH-CC could be used to diagnose pediatric cGvHD and whether the criteria operationalize well in a multi-institution study; (2) the frequency of cGvHD and L-aGvHD in children using the NIH-CC; and (3) the clinical features and risk factors for cGvHD and L-aGvHD using the NIH-CC...
May 1, 2019: Blood
https://read.qxmd.com/read/31043424/archeogenetics-of-f11-p-cys38arg-a-5-400-years-old-mutation-identified-in-different-southwestern-european-countries
#20
María Eugenia de la Morena-Barrio, Salam Salloum-Asfar, Julio Esteban, Belén de la Morena-Barrio, Carmen Altisent, Laura Martin-Fernandez, Paul Gueguen, Jose Padilla, Antonia Miñano, Rafael Parra, Vicente Vicente, Francisco Vidal, Frederic Bauduer, Pablo Carbonell, Javier Corral
No abstract text is available yet for this article.
May 1, 2019: Blood
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