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Haematologica

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https://www.readbyqxmd.com/read/28912177/rac1-functions-downstream-of-mir-142-in-regulation-of-erythropoiesis
#1
Natali Rivkin, Elik Chapnik, Yehudit Birger, Eran Yanowski, Caterina Curato, Alexander Mildner, Ziv Porat, Gail Amir, Shai Izraeli, Steffen Jung, Eran Hornstein
"-".
September 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28912176/anexelekto-mer-tyrosine-kinase-inhibitor-ono-7475-growth-arrests-and-kills-fms-like-tyrosine-kinase-3-internal-tandem-duplication-mutant-acute-myeloid-leukemia-cells-by-diverse-mechanisms
#2
Peter P Ruvolo, Huaxian Ma, Vivian R Ruvolo, Xiaorui Zhang, Hong Mu, Wendy Schober, Ivonne Hernandez, Miguel Gallardo, Joseph Khoury, Jorge Cortes, Michael Andreeff, Sean M Post
Nearly one-third of patients with acute myeloid leukemia have FMS-Like Tyrosine Kinase 3 mutations and thus have poor survival prospects. Receptor tyrosine kinase Anexelekto is critical for FMS-Like Tyrosine Kinase 3 signaling and participates in FMS-Like Tyrosine Kinase 3 inhibitor resistance mechanisms. Thus, strategies targeting Anexelekto could prove useful for acute myeloid leukemia therapy. ONO-7475 is an inhibitor with high specificity for Anexelekto and MER Tyrosine Kinase. Here we report that ONO-7475 potently arrested growth and induced apoptosis in acute myeloid leukemia with internal tandem duplication mutation of FMS-Like Tyrosine Kinase 3...
September 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28912175/in-vitro-evidence-of-complement-activation-in-patients-with-sickle-cell-disease
#3
Eleni Gavriilaki, Maria Mainou, Ioanna Christodoulou, Eudoxia-Evaggelia Koravou, Aggeliki Paleta, Tasoula Touloumenidou, Apostolia Papalexandri, Anastasia Athanasiadou, Chrysa Apostolou, Philippos Klonizakis, Achilles Anagnostopoulos, Efthymia Vlachaki
No abstract text is available yet for this article.
September 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28912174/senescence-is-a-spi1-pu-1-induced-anti-proliferative-mechanism-in-primary-hematopoietic-cells
#4
Laure Delestré, Cui Hengxiang, Michela Esposito, Cyril Quiveron, Elena Mylonas, Virginie Penard-Lacronique, Oliver Bischof, Christel Guillouf
Transcriptional deregulation caused by epigenetic or genetic alterations is a major cause of leukemic transformation. The Spi1/PU.1 transcription factor is a key regulator of many steps of hematopoiesis, and limits self-renewal of hematopoietic stem cells. The deregulation of its expression or activity contributes to leukemia, in which Spi1 can be either an oncogene or a tumor suppressor. Here, we explored whether cellular senescence, an anti-tumoral pathway that restrains cell proliferation, is a mechanism by which Spi1 limits hematopoietic cells expansion, and thus prevents the development of leukemia...
September 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28912173/secondary-malignant-neoplasms-progression-free-survival-and-overall-survival-in-patients-treated-for-hodgkin-lymphoma-a-systematic-review-and-meta-analysis-of-randomized-clinical-trials
#5
Dennis A Eichenauer, Ingrid Becker, Ina Monsef, Nicholas Chadwick, Vitaliana de Sanctis, Massimo Federico, Catherine Fortpied, Alessandro M Gianni, Michel Henry-Amar, Peter Hoskin, Peter Johnson, Stefano Luminari, Monica Bellei, Alessandro Pulsoni, Matthew R Sydes, Pinuccia Valagussa, Simonetta Viviani, Andreas Engert, Jeremy Franklin
Treatment intensification to maximize disease control and reduced-intensity approaches to minimize the risk of late sequelae have been evaluated in newly diagnosed Hodgkin lymphoma. The influence of these interventions on the risk of secondary malignant neoplasms, progression-free survival and overall survival is reported in the present meta-analysis based on individual patient data from 9498 patients treated within 16 randomized controlled trials for newly diagnosed Hodgkin lymphoma between 1984 and 2007. Secondary malignant neoplasms were meta-analyzed using Peto's method as time-to-event outcomes...
September 14, 2017: Haematologica
https://www.readbyqxmd.com/read/28883081/haploidentical-hematopoietic-cell-transplantation-for-adult-acute-myeloid-leukemia-a-position-statement-from-the-acute-leukemia-working-party-of-the-european-society-for-blood-and-marrow-transplantation
#6
Catherine J Lee, Bipin N Savani, Mohamad Mohty, Myriam Labopin, Annalisa Ruggeri, Christoph Schmid, Frédéric Baron, Jordi Esteve, Norbert C Gorin, Sebastian Giebel, Fabio Ciceri, Arnon Nagler
Allogeneic blood or marrow hematopoietic cell transplantation continues to be the most potent anti-leukemic treatment for adult patients with standard or high-risk, or chemo-refractory acute myeloid leukemia. Until recently, this procedure was generally limited to those recipients who had an available matched-sibling donor or matched-unrelated donor. Technical advances in graft cell processing and manipulation, control of bidirectional T cell alloreactivity, graft-versus-host disease prophylaxis, and other supportive measures in haploidentical transplantation now enables nearly all patients with acute myeloid leukemia to benefit from the graft-versus-leukemia effect with substantial reduction in procedure-related mortality...
September 7, 2017: Haematologica
https://www.readbyqxmd.com/read/28883080/phenotype-in-combination-with-genotype-improves-outcome-prediction-in-acute-myeloid-leukemia-a-report-from-children-s-oncology-group-protocol-aaml0531
#7
Andrew P Voigt, Lisa Eidenschink Brodersen, Todd A Alonzo, Robert B Gerbing, Andrew J Menssen, Elisabeth R Wilson, Samir Kahwash, Susana C Raimondi, Betsy A Hirsch, Alan S Gamis, Soheil Meshinchi, Denise A Wells, Michael R Loken
Diagnostic biomarkers can be used to determine relapse risk in acute myeloid leukemia, and certain genetic aberrancies have prognostic relevance. A diagnostic immunophenotypic expression profile, which quantifies the amounts of distinct gene products, not just their presence or absence, was established to improve outcome prediction for patients with acute myeloid leukemia. The immunophenotypic expression profile, which defines each patient's leukemia as a location in 15-dimensional space, was generated for 769 patients enrolled in the Children's Oncology Group AAML0531 protocol...
September 7, 2017: Haematologica
https://www.readbyqxmd.com/read/28883079/folate-dietary-insufficiency-and-folic-acid-supplementation-similarly-impair-metabolism-and-compromise-hematopoiesis
#8
Curtis J Henry, Travis Nemkov, Matias Casas-Selves, Ganna Bilousova, Vadym Zaberezhnyy, Kelly C Higa, Natalie J Serkova, Krik C Hansen, Angelo D' Alessandro, James DeGregori
While dietary folate deficiency is associated with increased risk for birth defects and other diseases, evidence suggests that supplementation with folic acid can contribute to predisposition to some diseases, including immune dysfunction and cancer. Here we show that diets supplemented with folic acid both below and above the recommended levels led to significantly altered metabolism in multiple tissues in mice. Surprisingly, both low and excessive dietary folate induced similar metabolic changes, which were particularly evident for nucleotide biosynthetic pathways in B-progenitor cells...
September 7, 2017: Haematologica
https://www.readbyqxmd.com/read/28883078/hla-e-mismatch-is-associated-with-better-hematopoietic-stem-cell-transplantation-outcome-in-acute-leukemia-patients
#9
Chrysanthi Tsamadou, Daniel Fürst, Vladan Vucinic, Donald Bunjes, Christine Neuchel, Daphne Mytilineos, Martin Gramatzki, Renate Arnold, Eva Maria Wagner, Hermann Einsele, Carlheinz Müller, Hubert Schrezenmeier, Joannis Mytilineos
The immunomodulatory role of HLA-E in hematopoietic stem cell transplantation (HSCT) has not been yet extensively investigated. To this end we genotyped 509 10/10 HLA unrelated transplant pairs for HLA-E, in order to study the effect of HLA-E as NK-alloreactivity mediator on HSCT outcome in an acute leukemia setting. Overall survival (OS), disease free survival (DFS), relapse incidence (RI) and non-relapse mortality (NRM) were set as endpoints. Analysis of our data revealed a significant correlation between HLA-E mismatch and improved HSCT outcome, as shown by both, univariate (53% vs 38%, p=0...
September 7, 2017: Haematologica
https://www.readbyqxmd.com/read/28860345/concurrent-diagnosis-of-crlf2-rearranged-and-ph-acute-lymphoblastic-leukemia-a-report-of-four-patients
#10
Nitin Jain, Xinyan Lu, Naval Daver, Beenu Thakral, Sa A Wang, Sergej Konoplev, Keyur Patel, Rashmi Kanagal-Shamanna, Marcus Valentine, Guilin Tang, Naveen Pemmaraju, Jeffrey Jorgensen, Partow Kebriaei, Cesar A Nunez, William Wierda, Elias Jabbour, Kathryn G Roberts, Charles G Mullighan, Hagop Kantarjian, Marina Konopleva
No abstract text is available yet for this article.
August 31, 2017: Haematologica
https://www.readbyqxmd.com/read/28860344/the-kinesin-spindle-protein-inhibitor-filanesib-enhances-the-activity-of-pomalidomide-and-dexamethasone-in-multiple-myeloma
#11
Susana Hernández-García, Laura San-Segundo, Lorena González-Méndez, Luis A Corchete, Irena Misiewicz-Krzeminska, Montserrat Martín-Sánchez, Ana-Alicia López-Iglesias, Esperanza-Macarena Algarín, Pedro Mogollón, Andrea Díaz-Tejedor, Teresa Paíno, Brian Tunquist, María-Victoria Mateos, Norma C Gutiérrez, Elena Díaz-Rodriguez, Mercedes Garayoa, Enrique M Ocio
Kinesin spindle protein inhibition is known to be an effective therapeutic approach in several malignancies. Filanesib (ARRY-520), an inhibitor if this proteins, has demonstrated activity in heavily pretreated multiple myeloma patients. The aim of this work was to investigate the activity of filanesib in combination with pomalidomide plus dexamethasone backbone, and the mechanisms underlying the potential synergistic effect.The ability of filanesib to enhance the activity of pomalidomide plus dexamethasone was studied in several in vitro and in vivo models...
August 31, 2017: Haematologica
https://www.readbyqxmd.com/read/28860343/antigen-receptor-sequencing-of-paired-bone-marrow-samples-shows-homogeneous-distribution-of-acute-lymphoblastic-leukemia-subclones
#12
Prisca M J Theunissen, David van Zessen, Andrew P Stubbs, Malek Faham, Michel Zwaan, Jacques J M van Dongen, Vincent H J Van der Velden
In B-cell precursor acute lymphoblastic leukemia, the initial leukemic cells share the same antigen receptor gene rearrangements. However, due to ongoing rearrangement processes, leukemic cells with different gene rearrangement patterns can develop, resulting in subclone formation. We studied leukemic subclones and their distribution in the bone marrow and peripheral blood at diagnosis. Antigen receptor gene rearrangements (IGH, IGK, TRG, TRD, TRB) were analyzed by next-generation sequencing in seven paired bone marrow samples and five paired bone marrow-blood samples...
August 31, 2017: Haematologica
https://www.readbyqxmd.com/read/28860342/cudc-907-in-relapsed-refractory-diffuse-large-b-cell-lymphoma-including-patients-with-myc-alterations-results-from-an-expanded-phase-1-trial
#13
Yasuhiro Oki, Kevin R Kelly, Ian Flinn, Manish R Patel, Robert Gharavi, Anna Ma, Jefferson Parker, Amir Hafeez, David Tuck, Anas Younes
CUDC-907 is a first-in-class, oral small molecule inhibitor of both HDAC (class I and II) and PI3K (class Iα, β, and δ) enzymes, with demonstrated anti-tumor activity in multiple preclinical models, including MYC-driven ones. In this report the safety and preliminary activity results of CUDC-907, with and without rituximab, in patients with relapsed/refractory diffuse large B-cell lymphoma are presented, with a particular focus on those with MYC-altered disease. Thirty-seven diffuse large B-cell lymphoma patients were enrolled, 14 with confirmed MYC-altered disease...
August 31, 2017: Haematologica
https://www.readbyqxmd.com/read/28860341/targeting-metabolism-and-survival-in-chronic-lymphocytic-leukemia-and-richter-syndrome-cells-by-a-novel-nf-kb-inhibitor
#14
Tiziana Vaisitti, Federica Gaudino, Samedy Ouk, Maria Moscvin, Nicoletta Vitale, Sara Serra, Francesca Arruga, Johannes L Zakrzewski, Hsiou-Chi Liou, John N Allan, Richard R Furman, Silvia Deaglio
IT-901 is a novel and selective NF-kB inhibitor with promising activity in pre-clinical models. Here we show that treatment of chronic lymphocytic leukemia cells with IT-901 effectively interrupts NF-kB transcriptional activity. Chronic lymphocytic leukemia cells exposed to the drug display elevated mitochondrial reactive oxygen species, which damage mitochondria, limit oxidative phosphorylation and ATP production and activate intrinsic apoptosis. Inhibition of NF-kB signaling in stromal and myeloid cells, both tumor-supportive elements, fails to induce apoptosis, but impairs NF-kB-driven expression of molecules involved in cell-cell contacts and immune responses, essential elements in creating a pro-leukemic niche...
August 31, 2017: Haematologica
https://www.readbyqxmd.com/read/28860340/impact-of-hospital-experience-on-the-quality-of-tyrosine-kinase-inhibitor-response-monitoring-and-consequence-for-chronic-myeloid-leukemia-patient-survival
#15
Inge G P Geelen, Noortje Thielen, Jeroen J W M Janssen, Mels Hoogendoorn, Tanja J A Roosma, Sten P Willemsen, Peter J M Valk, Otto Visser, Jan J Cornelissen, Peter E Westerweel
No abstract text is available yet for this article.
August 31, 2017: Haematologica
https://www.readbyqxmd.com/read/28860339/treatment-outcome-in-a-population-based-real-world-cohort-of-chronic-myeloid-leukemia-patients
#16
Inge G P Geelen, Noortje Thielen, Jeroen J W M Janssen, Mels Hoogendoorn, Tanja J A Roosma, Sten P Willemsen, Otto Visser, Jan J Cornelissen, Peter E Westerweel
Real-world evaluations of the efficacy and safety of tyrosine kinase inhibitors in patients with chronic myeloid leukemia are scarce. A nationwide population-based chronic myeloid leukemia registry was analyzed to evaluate (deep) response rates to first and subsequent treatment lines and eligibility for a treatment cessation attempt in adults diagnosed between January 2008 and April 2013 in the Netherlands. The registries covered 457 patients; 434 in chronic (95%) and 15 patients (3%) in advanced disease phase...
August 31, 2017: Haematologica
https://www.readbyqxmd.com/read/28860338/hif1a-is-a-critical-downstream-mediator-for-hemophagocytic-lymphohistiocytosis
#17
Rui Huang, Yoshihiro Hayashi, Xiaomei Yan, Jiachen Bu, Jieyu Wang, Yue Zhang, Yile Zhou, Yuting Tang, Lingyun Wu, Zefeng Xu, Xin Liu, Qianfei Wang, Jianfeng Zhou, Zhijian Xiao, James P Bridges, Rebecca A Marsh, Kejian Zhang, Michael B Jordan, Yuhua Li, Gang Huang
Hemophagocytic lymphohistiocytosis is a life-threatening syndrome characterized by overwhelming immune activation. A steroid and chemotherapy-based regimen remains as the first-line of therapy but it has substantial morbidity. Thus, novel, less toxic therapy for hemophagocytic lymphohistiocytosis is urgently needed. Although differences exist between familial hemophagocytic lymphohistiocytosis and secondary hemophagocytic lymphohistiocytosis, they have many common features. Using bioinformatic analysis with familial hemophagocytic lymphohistiocytosis and systemic juvenile idiopathic arthritis, which is associated with secondary hemophagocytic lymphohistiocytosis, we identified a common hypoxia-inducible factor 1A (HIF1A) signature...
August 31, 2017: Haematologica
https://www.readbyqxmd.com/read/28838995/mass-spectrometry-based-identification-of-a-naturally-presented-receptor-tyrosine-kinase-like-orphan-receptor-1-derived-epitope-recognized-by-cd8-cytotoxic-t-cells
#18
Falk Heidenreich, Elke Rücker-Braun, Juliane S Walz, Anne Eugster, Denise Kühn, Sevina Dietz, Annika Nelde, Antje Tunger, Rebekka Wehner, Cornelia S Link, Jan M Middeke, Friedrich Stölzel, Torsten Tonn, Stefan Stevanovic, Hans-Georg Rammensee, Ezio Bonifacio, Michael Bachmann, Matthias Zeis, Gerhard Ehninger, Martin Bornhäuser, Johannes Schetelig, Marc Schmitz
No abstract text is available yet for this article.
August 24, 2017: Haematologica
https://www.readbyqxmd.com/read/28838994/the-btk-inhibitor-cc-292-shows-activity-in-mantle-cell-lymphoma-and-synergizes-with-lenalidomide-and-nik-inhibitors-depending-on-the-nf-%C3%AE%C2%BAb-mutational-status
#19
Anna Vidal-Crespo, Vanina Rodriguez, Alba Matas-Céspedes, Eriong Lee, Alfredo Rivas-Delgado, Eva Giné, Alba Navarro, Sílvia Beà, Elías Campo, Armando López-Guillermo, Mónica López-Guerra, Gaël Roué, Dolors Colomer, Patricia Pérez-Galán
No abstract text is available yet for this article.
August 24, 2017: Haematologica
https://www.readbyqxmd.com/read/28838993/prognostic-discrimination-based-on-the-eutos-long-term-survival-score-within-the-international-registry-for-chronic-myeloid-leukemia-in-children-and-adolescents
#20
Frédéric Millot, Joëlle Guilhot, Meinolf Suttorp, Adalet Maral Güneş, Petr Sedlacek, Evelyn De Bont, Chi Kong Li, Krzysztof Kalwak, Birgitte Lausen, Srdjana Culic, Michael Dworzark, Emilia Kaiserova, Barbara De Moerloose, Farah Roula, Andrea Biondi, André Baruchel
The EUTOS Long Term Survival score was tested in 350 children with chronic myeloid leukemia in first chronic phase treated with imatinib and registered in the International Registry for Childhood Chronic Myeloid Leukemia. With a median follow up of 3 years (range 1 month to 6 years) progression and/or death (whichever came first) occurred in 23 patients. For the entire cohort of patients the 5 year progression free survival was 92% (95% CI: 87%-94%) and 5 year survival accounting for chronic myeloid leukemia death was 97% (95% CI: 94%-99%)...
August 24, 2017: Haematologica
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