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Katrien Van Roosbroeck, Recep Bayraktar, Steliana Calin, Johannes Bloehdorn, Mihnea Paul Dragomir, Keishi Okubo, Maria Teresa Sabrina Bertilaccio, Simonetta Zupo, M James You, Gianluca Gaidano, Davide Rossi, Shih-Shih Chen, Nicholas Chiorazzi, Philip Thompson, Alessandra Ferrajoli, Francesco Bertoni, Stephan Stilgenbauer, Michael J Keating, George A Calin
Richter syndrome represents the transformation of the most frequent type of leukemia, chronic lymphocytic leukemia into an aggressive lymphoma. Patients with Richter syndrome have limited response to therapies and dismal survival. The underlying mechanisms of transformation are insufficiently understood and there is a major lack of knowledge regarding the roles of microRNAs that have already proved to be causative for most cases of chronic lymphocytic leukemia. Here, by using four types of genomic platforms and independent sets of patients from three institutions, we identified microRNAs involved in the transformation of chronic lymphocytic leukemia to Richter syndrome...
November 8, 2018: Haematologica
Anna B Halpern, Megan Othus, Emily M Huebner, Bart L Scott, Paul C Hendrie, Mary-Elizabeth M Percival, Pamela S Becker, Heather A Smith, Vivian G Oehler, Johnnie J Orozco, Ryan D Cassaday, Kelda M Gardner, Tara L Chen, Sarah A Buckley, Kaysey F Orlowski, Asma Anwar, Elihu H Estey, Roland B Walter
No abstract text is available yet for this article.
November 8, 2018: Haematologica
Roberto Bernardoni, Giorgia Giordani, Elisabetta Signorino, Sara Monticelli, Francesca Messa, Monica Pradotto, Valentina Rosso, Enrico Bracco, Angela Giangrande, Giovanni Perini, Giuseppe Saglio, Daniela Cilloni
The oncoprotein BCR-ABL1 triggers Chronic Myeloid Leukemia. It is clear that the disease relies on the constitutive BCR-ABL1 kinase activity, but not all the interactors and regulators of the oncoprotein are known. We describe and validate a Drosophila leukemia model based on inducible human BCR-ABL1 expression controlled by tissue specific promoters and thought as a versatile tool to perform genetic screens. BCR-ABL1 expression in the developing eye interferes with ommatidia differentiation and expression in the hematopoietic precursors increases the number of circulating blood cells...
November 8, 2018: Haematologica
Beatrice Drexler, Jakob R Passweg, Alexandar Tzankov, Martin Bigler, Alexandre P A Theocharides, Nathan Cantoni, Peter Keller, Georg Stussi, Axel Ruefer, Rudolf Benz, Geneviève Favre, Pontus Lundberg, Ronny Nienhold, Andrea Fuhrer, Christine Biaggi, Markus G Manz, Mario Bargetzi, Simon Mendez-Ferrer, Radek C Skoda
The β-3 sympathomimetic agonist BRL37344 restored nestin-positive cells within the stem cell niche, and thereby normalized blood counts and improved myelofibrosis in a mouse model of JAK2-V617F positive myeloproliferative neoplasms. We therefore tested the effectiveness of mirabegron, a β-3 sympathomimetic agonist, in a phase II trial including 39 JAK2-V617F positive MPN with a mutant allele burden >20%. Treatment consisted of mirabegron 50 mg daily for 24 weeks. The primary endpoint, reduction of the JAK2-V617F allele burden ≥50%, was not reached in any of the patients...
November 8, 2018: Haematologica
Courtney J Mercadante, Milankumar Prajapati, Jignesh H Parmar, Heather L Conboy, Miriam E Dash, Michael A Pettiglio, Carolina Herrera, Julia T Bu, Edward G Stopa, Pedro Mendes, Thomas B Bartnikas
The current paradigm in the field of mammalian iron biology states that body iron levels are determined by dietary iron absorption, not by iron excretion. Iron absorption is a highly regulated process influenced by iron levels and other factors. Iron excretion is believed to occur at a basal rate irrespective of iron levels and is associated with processes such as turnover of intestinal epithelium, blood loss, and exfoliation of dead skin. Here we explore iron excretion in a mouse model of iron excess due to inherited transferrin deficiency...
November 8, 2018: Haematologica
Anna Stengel, Sabine Jeromin, Torsten Haferlach, Manja Meggendorfer, Wolfgang Kern, Claudia Haferlach
No abstract text is available yet for this article.
November 8, 2018: Haematologica
Anton Hagenbeek, Hans Mooij, Josée Zijlstra, Pieternella Lugtenburg, Gustaaf Van Imhoff, Marcel Nijland, Sanne Tonino, Martin Hutchings, Marjolein Spiering, Roberto Liu, Harm Van Tinteren, Marie-José Kersten
No abstract text is available yet for this article.
October 31, 2018: Haematologica
Lionel Ades, Agnès Guerci-Bresler, Pascale Cony-Makhoul, Laurence Legros, Marie Sebert, Thosten Braun, Jacques Delaunay, Kristell Desseaux, Sylvie Chevret, Pierre Fenaux
No abstract text is available yet for this article.
October 31, 2018: Haematologica
Regula Burkhard, Irene Keller, Miroslav Arambasic, Darius Juskevicius, Alexandar Tzankov, Pontus Lundberg, Rémy Bruggman, Stephan Dirnhofer, Ramin Radpour, Urban Novak
Diffuse large B-cell lymphoma is the most common malignant lymphoma in adults. By gene-expression profiling, this lymphoma is divided in three cell-of-origin subtypes with distinct molecular and clinical features. Most lymphomas arise sporadically, yet familial clustering is known, suggesting a genetic contribution to disease risk. Familial lymphoma cases are a valuable tool to investigate risk genes. We studied a Swiss/Japanese family with two sisters affected by a primary mediastinal B-cell lymphoma and a non-germinal center diffuse large B-cell lymphoma not otherwise specified, respectively...
October 31, 2018: Haematologica
Paresh P Kulkarni, Arundhati Tiwari, Nitesh Singh, Deepa Gautam, Vijay K Sonkar, Vikas Agarwal, Debabrata Dash
Platelets are critical to arterial thrombosis that underlies myocardial infarction and stroke. Activated platelets, regardless of nature of stimulus, initiate energy-intensive processes that sustain thrombus, while adapting to potential adversities of hypoxia and nutrient deprivation within the densely packed thrombus milieu. We report here that stimulated platelets switch their energy metabolism to aerobic glycolysis by modulating enzymes at key checkpoints in glucose metabolism. We found aerobic glycolysis to, in turn, accelerate flux through pentose phosphate pathway and support platelet activation...
October 31, 2018: Haematologica
Roel Polak, Marc B Bierings, Cindy S van der Leije, Mathijs A Sanders, Onno Roovers, Joao R M Marchante, Judith M Boer, Jan J Cornelissen, Rob Pieters, Monique L den Boer, Miranda Buitenhuis
Translocation t(12;21), resulting in the ETV6-RUNX1 (or TEL-AML1) fusion protein, is present in 25% of pediatric patients with B-cell precursor acute lymphoblastic leukemia and is considered a first hit in leukemogenesis. A targeted therapy approach is not available for children with this subtype of leukemia. To identify the molecular mechanisms underlying ETV6-RUNX1 driven leukemia, we performed gene expression profiling of healthy hematopoietic progenitors in which we ectopically expressed ETV6-RUNX1. We reveal an ETV6-RUNX1 driven transcriptional network that induces proliferation, survival and cellular homeostasis...
October 31, 2018: Haematologica
Michael A Pulsipher, Brent R Logan, Deidre M Kiefer, Pintip Chitphakdithai, Marcie L Riches, J Douglas Rizzo, Paolo Anderlini, Susan F Leitman, Hati Kobusingye, RaeAnne M Besser, John P Miller, Rebecca J Drexler, Aly Abdel-Mageed, Ibrahim A Ahmed, Luke P Akard, Andrew S Artz, Edward D Ball, Ruthee-Lu Bayer, Carolyn Bigelow, Brian J Bolwell, E Randolph Broun, David C Delgado, Katharine Duckworth, Christopher C Dvorak, Theresa E Hahn, Ann E Haight, Parameswaran N Hari, Brandon M Hayes-Lattin, David A Jacobsohn, Ann A Jakubowski, Kimberly A Kasow, Hillard M Lazarus, Jane L Liesveld, Michael Linenberger, Mark R Litzow, Walter Longo, Margarida Magalhaes-Silverman, John M McCarty, Joseph P McGuirk, Shahram Mori, Vinod Parameswaran, Vinod K Prasad, Scott D Rowley, Witold B Rybka, Indira Sahdev, Jeffrey R Schriber, George B Selby, Paul J Shaughnessy, Shalini Shenoy, Thomas Spitzer, William T Tse, Joseph P Uberti, Madhuri Vusirikala, Edmund K Waller, Daniel J Weisdorf, Gregory A Yanik, Willis H Navarro, Mary M Horowitz, Galen E Switzer, Dennis L Confer, Bronwen E Shaw
Unlike unrelated donor registries, transplant centers lack uniform approaches to related donor assessment and deferral. To test whether related donors are at increased risk for donation related toxicities we conducted a prospective observational trial of 11,942 related and unrelated age 18-60. Bone marrow was collected at 37 transplant and 78 National Marrow Donor Program centers and peripheral blood stem cells were collected at 42 transplant and 87 unrelated donor centers in North America. Ascertainment of medical comorbidities occurred prior to donation and standardized pain and toxicity measures were assessed pre-donation, peri-donation, and one year following...
October 31, 2018: Haematologica
Maria Rosaria Sapienza, Francesco Abate, Federica Melle, Stefania Orecchioni, Fabio Fuligni, Maryam Etebari, Valentina Tabanelli, Maria Antonella Laginestra, Alessandro Pileri, Giovanna Motta, Maura Rossi, Claudio Agostinelli, Elena Sabattini, Nicola Pimpinelli, Mauro Truni, Brunangelo Falini, Lorenzo Cerroni, Giovanna Talarico, Rossana Piccioni, Stefano Amente, Valentina Indio, Giuseppe Tarantino, Francesco Brundu, Marco Paulli, Emilio Berti, Fabio Facchetti, Gaetano Ivan Dellino, Francesco Bertolini, Claudio Tripodo, Raul Rabadan, Stefano A Pileri
Blastic Plasmacytoid Dendritic Cell Neoplasm is a rare and aggressive hematological malignancy currently lacking an effective therapy. To possibly identify genetic alterations useful for a new treatment design, we analyzed by whole-exome sequencing fourteen Blastic Plasmacytoid Dendritic Cell Neoplasm patients and the patient-derived CAL-1 cell line. The functional enrichment analysis of mutational data reported the epigenetic regulatory program as the most significantly undermined (P<.0001). In particular, twenty-five epigenetic-modifiers were found mutated (e...
October 31, 2018: Haematologica
Annas Al-Sharea, Man K S Lee, Alexandra Whillas, Danielle Michell, Waled Shihata, Alyce J Nicholls, Olivia D Cooney, Michael J Kraakman, Camilla Bertuzzo Veiga, Ann-Maree Jefferis, Kristy Jackson, Prabhakara R Nagareddy, Gavin Lambert, Connie H Y Wong, Karen L Andrews, Geoff A Head, Jaye Chin-Dusting, Andrew J Murphy
Hypertension is a major, independent risk factor for atherosclerotic cardiovascular disease. However, this pathology can arise through multiple pathways, which could influence vascular disease through distinct mechanisms. An overactive sympathetic nervous system is a dominant pathway that can precipitate in elevated blood pressure. We aimed to determine how the sympathetic nervous system directly promotes atherosclerosis in the setting of hypertension. We used a mouse model of sympathetic nervous system-driven hypertension on the atherosclerotic-prone apolipoprotein E deficient background...
October 25, 2018: Haematologica
Nina Borràs, Gerard Orriols, Javier Batlle, Almudena Pérez-Rodríguez, Teresa Fidalgo, Patricia Martinho, María Fernanda López-Fernández, Ángela Rodríguez-Trillo, Esther Lourés, Rafael Parra, Carme Altisent, Ana Rosa Cid, Santiago Bonanad, Noelia Cabrera, Andrés Moret, María Eva Mingot-Castellano, Nira Navarro, Rocío Pérez-Montes, Sally Marcellini, Ana Moreto, Sonia Herrero, Inmaculada Soto, Núria Fernández-Mosteirín, Víctor Jiménez-Yuste, Nieves Alonso, Aurora de Andrés-Jacob, Emilia Fontanes, Rosa Campos, María José Paloma, Nuria Bermejo, Ruben Berrueco, José Mateo, Karmele Arribalzaga, Pascual Marco, Ángeles Palomo, Nerea Castro Quismondo, Belén Iñigo, María Del Mar Nieto, Rosa Vidal, María Paz Martínez, Reyes Aguinaco, Jesús María Tenorio, María Ferreiro, Javier García-Frade, Ana María Rodríguez-Huerta, Jorge Cuesta, Ramón Rodríguez-González, Faustino García-Candel, Manuela Dobón, Carlos Aguilar, Francisco Vidal, Irene Corrales
Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques...
October 25, 2018: Haematologica
Evgeniya Angelova, Charlene Audette, Yelena Kovtun, Naval Daver, Sa A Wang, Sherry Pierce, Sergej N Konoplev, Haitham Khogeer, Jeffrey L Jorgensen, Marina Konopleva, Patrick A Zweidler-McKay, L Jeffrey Medeiros, Hagop M Kantarjian, Elias J Jabbour, Joseph D Khoury
The potential of CD123-targeted therapies in acute lymphoblastic leukemia/lymphoma remains largely unexplored. We examined CD123 expression levels in a large cohort of acute lymphoblastic leukemia/lymphoma patients and assessed the in vitro impact of IMGN632, a conjugate of CD123-binding antibody with a novel DNA-alkylating payload. CD123 expression on leukemic blasts was surveyed in a large cohort of acute lymphoblastic leukemia/lymphoma patients using multicolor/multiparameter flow cytometry. The in vitro effect of IMGN632 was evaluated on B acute lymphoblastic leukemia/lymphoma cell lines and primary B acute lymphoblastic leukemia/lymphoma blasts...
October 25, 2018: Haematologica
Erik Arnaud, Camille Soulier, Jean-Christophe Gris
No abstract text is available yet for this article.
October 25, 2018: Haematologica
Eolia Brissot, Myriam Labopin, Gerhard Ehninger, Matthias Stelljes, Arne Brecht, Arnold Ganser, Johanna Tischer, Nicolaus Kröger, Boris Afanasyev, Jürgen Finke, Ahmet Elmaagacli, Hermann Einsele, Mohamad Mohty, Arnon Nagler
Primary refractory or relapsed acute myeloid leukemia is associated with dismal prognosis. Allogeneic stem cell transplantation is the only therapeutic option that offers prolonged survival and cure in this setting. In the absence of a matched sibling donor, transplantation from unrelated 10/10 or 9/10 and haploidentical donors are potential alternatives. The current study aimed to compare the outcomes of acute myeloid leukemia patients with active disease who received allogeneic stem cell transplantation from a haploidentical donor with post-transplant cyclophosphamide (n=199) versus an unrelated donor 10/10 (n=1111) and versus unrelated donor 9/10 (n=383) between 2007 and 2014 and reported to the EBMT registry...
October 25, 2018: Haematologica
Arantza Onaindia, Sonia González de Villambrosía, Lucía Prieto-Torres, Socorro M Rodríguez-Pinilla, Santiago Montes-Moreno, Carmen González-Vela, Miguel A Piris
No abstract text is available yet for this article.
October 25, 2018: Haematologica
Phuong M Le, Michael Andreeff, Venkata Lokesh Battula
The bone marrow microenvironment, also known as the bone marrow niche, is a complex network of cell types and acellular factors that supports normal hematopoiesis.. For many years, leukemia was believed to be caused by a series of genetic hits to hematopoietic stem and progenitor cells, which transform them to preleukemic and eventually to leukemic cells. Recent discoveries suggest that genetic alterations in bone marrow niche cells, particularly in osteogenic cells, may also cause myeloid leukemia in mouse models...
October 18, 2018: Haematologica
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