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Marie de Charette, Roch Houot
Evading immune eradication is a pre-request for neoplastic progression and one of the hallmarks of cancer. Here, we review the different immune escape strategies of lymphoma and classify them into two main mechanisms. First, lymphoma cells may "hide" to become invisible to the immune system. This can be achieved by losing or down-regulating MHC and/or molecules involved in antigen presentation (including antigen processing machinery and adhesion molecules), thereby preventing their recognition by the immune system...
July 13, 2018: Haematologica
Pierre Bories, Sébastien Lamy, Célestine Simand, Sarah Bertoli, Cyrille Delpierre, Sandra Malak, Luc Fornecker, Stéphane Moreau, Christian Récher, Antoine Nebout
Elderly patients with acute myeloid leukemia can be treated with intensive chemotherapy, low-intensity therapy such as low-dose aracytine or hypomethylating agents, or best supportive care. The choice between these treatments is a function of many patient-related and physician-related factors. We investigated how physicians' behavioral characteristics, in particular their attitudes towards risk and uncertainty affect medical decision-making between intensive and non-intensive therapy in this setting. A nationwide cross-sectional online survey of hematologists collected data on medical decision-making for six clinical vignettes involving older acute myeloid leukemia patients that were representative of routine practice...
July 13, 2018: Haematologica
Simon Berhe, Matthew M Heeney, Dean R Campagna, John F Thompson, Eric J White, Tristen Ross, Roy Wa Peake, Jeffery D Hanrahan, Vilmarie Rodriguez, Deborah L Renaud, Mrinal S Patnaik, Eugenia Chang, Sylvia S Bottomley, Mark D Fleming
No abstract text is available yet for this article.
July 13, 2018: Haematologica
Bryan C Hambley, Rania Abdul Rahman, Maxwell Reback, Mary Ann O'Riordan, Nathan Langer, Robert C Gilkeson, Mahazarin Ginwalla, Jane A Little, Robert Schilz
No abstract text is available yet for this article.
July 13, 2018: Haematologica
Justyna Chlebowska-Tuz, Olga Sokolowska, Pawel Gaj, Michal Lazniewski, Malgorzata Firczuk, Karolina Borowiec, Hanna Sas-Nowosielska, Malgorzata Bajor, Agata Malinowska, Angelika Muchowicz, Kavita Ramji, Piotr Stawinski, Mateusz Sobczak, Zofia Pilch, Anna Rodziewicz-Lurzynska, Malgorzata Zajac, Krzysztof Giannopoulos, Przemyslaw Juszczynski, Grzegorz W Basak, Dariusz Plewczynski, Rafal Ploski, Jakub Golab, Dominika Nowis
Acute myeloid leukemia is a malignant disease of immature myeloid cells. Despite significant therapeutic effects of differentiation-inducing agents in some acute myeloid leukemia subtypes, the disease remains incurable in a large fraction of patients. Here, we show that SK053, a thioredoxin inhibitor, induces differentiation and cell death of acute myeloid leukemia cells. Considering that thioredoxin knock-down with short hairpin RNA failed to exert antiproliferative effects in one of the acute myeloid leukemia cell lines we have used a biotin affinity probe-labeling approach to identify potential molecular targets for SK053 effects...
July 12, 2018: Haematologica
Jesse D Lai, Laura L Swystun, Dominique Cartier, Kate Nesbitt, Cunjie Zhang, Christine Hough, James W Dennis, David Lillicrap
Immune responses to factor VIII remain the greatest complication in the treatment of severe hemophilia A. Recent epidemiological evidence has highlighted that recombinant factor VIII produced in baby hamster kidney cells is more immunogenic than factor VIII produced in Chinese hamster ovary cells. Glycosylation differences have been hypothesized to influence the immunogenicity of these synthetic concentrates. In two hemophilia A mouse models, baby hamster kidney cell-derived factor VIII elicited a stronger immune response compared Chinese hamster ovary cell-derived factor VIII...
July 12, 2018: Haematologica
Chandran Ka, Julie Guellec, Xavier Perpermans, Caroline Kannengiesser, Cécile Ged, Wim Wuyts, David Cassiman, Victor de Ledinghen, Bruno Varet, Caroline de Kerguenec, Claire Oudin, Isabelle Gourlaouen, Thibaud Lefebvre, Claude Férec, Isabelle Callebaut, Gerald Le Gac
Hemochromatosis type 4 is one of the commonest causes of primary iron overload, after HFE-related hemochromatosis. It is an autosomal dominant disorder, primarily due to missense mutations in SLC40A1. This gene encodes ferroportin 1 (FPN1), which is the sole iron export protein reported in mammals. Not all heterozygous missense mutations in SLC40A1 are disease-causing. Due to phenocopies and increased demand for genetic testing, rare SLC40A1 variations are fortuitously observed in patients with a secondary cause of hyperferritinemia...
July 12, 2018: Haematologica
Diego Villa, Laurie H Sehn, Christina Aquino-Parsons, Petter Tonseth, David W Scott, Alina S Gerrie, Donald Wilson, François Bénard, Randy D Gascoyne, Graham W Slack, Pedro Farinha, James Morris, Tom Pickles, Joseph M Connors, Kerry J Savage
No abstract text is available yet for this article.
July 12, 2018: Haematologica
Brent A Williams, Xing-Hua Wang, Jeffrey V Leyton, Sonam Maghera, Bishoy Deif, Raymond M Reilly, Mark D Minden, Armand Keating
Patients with acute myeloid leukemia often relapse after initial therapy, because of persistence of leukemic stem cells which frequently express the IL-3 receptor alpha chain CD123. Natural killer cell-based therapeutic strategies for acute myeloid leukemia show promise and we explore the NK cell lines, NK-92 and CD16+NK-92, as a treatment for acute myeloid leukemia. NK-92 has been tested in phase I clinical trials with minimal toxicity; irradiation prior to infusion prevents risk of engraftment. The CD16 negative NK-92 parental line was genetically modified to express the high affinity Fc gamma receptor, enabling antibody-dependent cell-mediated cytotoxicity, which we utilized in combination with an anti-CD123 antibody to target leukemic stem cells...
July 5, 2018: Haematologica
Katja Seipel, Miguel A T Marques, Corinne Sidler, Beatrice U Mueller, Thomas Pabst
Prognosis for FLT3-ITD positive acute myeloid leukemia with high allelic ratio (>0.5) is poor, particularly in relapse, refractory to or unfit for intensive treatment, thus highlighting an unmet need for novel therapeutic approaches. The combined use of compounds targeting both the mutated FLT3 receptor and cellular p53 inhibitors might be a promising treatment option for this poor risk leukemia subset. We therefore assessed MDM2 and FLT3 inhibitors as well as cytotoxic compounds used for conventional induction treatment as single agents and in combination for their ability to induce apoptosis and cell death in leukemic cells...
July 5, 2018: Haematologica
Alan K Burnett, Emma Das Gupta, Steve Knapper, Asim Khwaja, Marion Sweeney, Lars Kjeldsen, Timothy Hawkins, Sophie E Betteridge, Paul Cahalin, Richard E Clark, Robert K Hills, Nigel H Russell
As part of the UK NCRI AML17 trial, adult acute myeloid leukaemia patients in remission could be randomised to receive the mTOR inhibitor everolimus, sequentially with post-induction chemotherapy. Three hundred and thirty-nine patients were randomised (2:1) to receive everolimus or not for a maximum of 84 days between chemotherapy courses. The primary endpoint was relapse free survival (RFS). At 5 years there was no difference in Relapse Free Survival (29% vs 40%; OR 1.19 (0.9-1.59) p=0.2), cumulative incidence of relapse (60% vs 54%: OR 1...
July 5, 2018: Haematologica
Ilaria S Pagani, Phuong Dang, Ivar O Kommers, Jarrad M Goyne, Mario Nicola, Verity A Saunders, Jody Braley, Deborah L White, David T Yeung, Susan Branford, Timothy P Hughes, David M Ross
Accurate quantification of minimal residual disease during treatment of chronic myeloid leukaemia guides clinical decisions. The conventional minimal residual disease method, RQ-PCR for BCR-ABL1 mRNA, reflects a composite of the number of circulating leukemic cells and the BCR-ABL1 transcripts per cell. BCR-ABL1 genomic DNA only reflects leukemic cell number. We used both methods in parallel to determine the relative contribution of the leukemic cell number to molecular response. BCR-ABL1 DNA PCR and RQ-PCR were monitored up to 24 months in 516 paired samples from 59 newly-diagnosed patients treated with first-line imatinib in the TIDEL-II study...
July 5, 2018: Haematologica
Takashi Toya, Mizuki Ogura, Kazuhiro Toyama, Akihide Yoshimi, Aya Shinozaki-Ushiku, Akira Honda, Kenjiro Honda, Noriko Hosoya, Yukako Murakami, Hiroyuki Kawashima, Yasuhito Nannya, Shunya Arai, Fumihiko Nakamura, Yusuke Shinoda, Masaomi Nangaku, Kiyoshi Miyagawa, Masashi Fukayama, Akiko Moriya-Saito, Ichiro Katayama, Takashi Ogura, Mineo Kurokawa
Erdheim-Chester disease is a rare histiocytosis with insufficient clinical data. To clarify the clinical features and prognostic factors of Erdheim-Chester disease, we conducted a nationwide survey to collect the detailed data of 44 patients with Erdheim-Chester disease in Japan. The median age of onset of the participants was 51 (range: 23-76) years, and the median number of involved organs per patient was 4 (range: 1&-11). The existence of central nervous system disease was correlated with older age (p = 0...
July 5, 2018: Haematologica
Véronique Leblond, Melih Aktan, Christelle M Ferra Coll, Caroline Dartigeas, Jens Kisro, Marco Montillo, João Raposo, Jean-Louis Merot, Susan Robson, Ekaterina Gresko, Francesc Bosch, Stephan Stilgenbauer, Robin Foà
The safety of obinutuzumab, alone or with chemotherapy, was studied in a non-randomized, open-label, non-comparative, Phase 3b study (GREEN) in previously untreated or relapsed/refractory chronic lymphocytic leukemia. Patients received obinutuzumab 1000 mg, alone or with chemotherapy (investigator's choice of fludarabine-cyclophosphamide for fit patients, chlorambucil for unfit patients or bendamustine for any patient), on day 1, 8 and 15 of cycle 1, and day 1 of cycles 2-6 (28-day cycles), with the cycle 1/day 1 dose administered over 2 days...
July 5, 2018: Haematologica
Jennifer E Adair, Devikha Chandrasekaran, Gabriella Sghia-Hughes, Kevin G Haworth, Ann E Woolfrey, Lauri M Burroughs, Grace Y Choi, Pamela S Becker, Hans-Peter Kiem
A hallmark of Fanconi anemia is accelerated decline in hematopoietic stem and progenitor cells (CD34+) leading to bone marrow failure. Long-term treatment requires hematopoietic cell transplantation from an unaffected donor but is associated with potentially severe side effects. Gene therapy to correct the genetic defect in the patient's own CD34+ cells has been limited by low CD34+ cell numbers and viability. Here we demonstrate an altered ratio of CD34Hi to CD34Lo cells in Fanconi patients relative to healthy donors, with exclusive in vitro repopulating ability in only CD34Hi cells, underscoring a need for novel strategies to preserve limited CD34+ cells...
July 5, 2018: Haematologica
Kevin Gaffney, Michael Weinberg, Maira Soto, Stan Louie, Kathleen Rodgers
No abstract text is available yet for this article.
July 5, 2018: Haematologica
Shamzah Araf, Jun Wang, Margaret Ashton-Key, Koorosh Korfi, Doriana Di Bella, Ana Rio-Machin, Mariette Odabashian, Vipul Foria, Ming-Qing Du, Francesco Cucco, Sharon Barrans, Peter Johnson, Sophie R Laird, Andrew M Fisher, Jonathan O Cullis, Trevor A Graham, Jessica Okosun, Jude Fitzgibbon, Laura Chiecchio
No abstract text is available yet for this article.
July 5, 2018: Haematologica
Frances Smith, Sila Hopton, Cristina Dallabona, Micol Gilberti, Gavin Falkous, Fiona Norwood, Claudia Donnini, Gráinne S Gorman, Barnaby Clark, Robert W Taylor, Austin G Kulasekararaj
No abstract text is available yet for this article.
July 5, 2018: Haematologica
Lynne V Abruzzo, Carmen D Herling, George A Calin, Christopher Oakes, Lynn L Barron, Haley E Banks, Vikram Katju, Michael J Keating, Kevin R Coombes
Although +12 chronic lymphocytic leukemia comprises about 20% of cases, relatively little is known about its pathophysiology. These cases often demonstrate atypical morphologic and immunophenotypic features, high proliferative rates, unmutated immunoglobulin heavy chain variable region genes, and a high frequency of NOTCH1 mutation. Patients with +12 chronic lymphocytic leukemia have an intermediate prognosis, and show higher incidences of thrombocytopenia, Richter's transformation, and other second cancers...
July 5, 2018: Haematologica
Silvia Martinelli, Rossana Maffei, Stefania Fiorcari, Chiara Quadrelli, Patrizia Zucchini, Stefania Benatti, Leonardo Potenza, Mario Luppi, Roberto Marasca
No abstract text is available yet for this article.
July 5, 2018: Haematologica
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