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Haematologica

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https://www.readbyqxmd.com/read/28642303/molecular-analysis-of-myelodysplastic-syndrome-with-isolated-del-5q-reveals-a-specific-spectrum-of-molecular-mutations-with-prognostic-impact-a-study-on-123-patients-and-27-genes
#1
Manja Meggendorfer, Claudia Haferlach, Wolfgang Kern, Torsten Haferlach
The only cytogenetic aberration defining a myelodysplastic syndrome subtype is the deletion of the long arm of chromosome 5, giving with morphological features the diagnosis of myelodysplastic syndrome with isolated del(5q). These patients show a good prognosis and respond to treatment such as lenalidomide, but some cases progress to acute myeloid leukemia. However, the molecular mutation pattern is rarely characterized. Therefore, we investigated a large cohort of 123 myelodysplastic syndrome patients with isolated del(5q) diagnosed following the World Health Organization classifications 2008 and 2016 by sequencing 27 genes...
June 22, 2017: Haematologica
https://www.readbyqxmd.com/read/28642302/residual-erythropoiesis-protects-against-myocardial-hemosiderosis-in-transfusion-dependent-thalassemia-by-lowering-labile-plasma-iron-via-transient-generation-of-apotransferrin
#2
Maciej W Garbowski, Patricia Evans, Evangelia Vlachodimitropoulou, Robert Hider, John B Porter
Cardiosiderosis is a leading cause of mortality in transfusion-dependent thalassemias. Plasma non-transferrin-bound iron and its redox-active component, labile plasma iron, are key sources of iron loading in cardiosiderosis. Risk factors were identified in 73 patients with or without cardiosiderosis. Soluble transferrin receptor-1 levels were significantly lower in patients with cardiosiderosis (odds ratio 21). This risk increased when transfusion-iron loading rates exceeded the erythroid transferrin uptake rate (derived from soluble transferrin receptor-1) by >0...
June 22, 2017: Haematologica
https://www.readbyqxmd.com/read/28642301/the-specific-btk-inhibitor-acalabrutinib-acp-196-shows-favorable-in-vitro-activity-against-chronic-lymphocytic-leukemia-b-cells-with-cd20-antibodies
#3
Josée Golay, Greta Ubiali, Martino Introna
No abstract text is available yet for this article.
June 22, 2017: Haematologica
https://www.readbyqxmd.com/read/28642300/center-level-variation-in-accuracy-of-adverse-event-reporting-in-a-clinical-trial-for-pediatric-acute-myeloid-leukemia-a-report-from-the-children-s-oncology-group
#4
Tamara P Miller, Yimei Li, Marko Kavcic, Kelly D Getz, Yuan-Shun V Huang, Lillian Sung, Todd A Alonzo, Robert Gerbing, Marla H Daves, Terzah M Horton, Michael A Pulsipher, Jessica Pollard, Rochelle Bagatell, Alix E Seif, Brian T Fisher, Selina Luger, Alan S Gamis, Peter C Adamson, Richard Aplenc
No abstract text is available yet for this article.
June 22, 2017: Haematologica
https://www.readbyqxmd.com/read/28619848/red-blood-cell-gardos-channel-kcnn4-the-essential-determinant-of-erythrocyte-dehydration-in-hereditary-xerocytosis
#5
Raphaël Rapetti-Mauss, Véronique Picard, Corinne Guitton, Khaldoun Ghazal, Valérie Proulle, Catherine Badens, Olivier Soriani, Loïc Garçon, Hélène Guizouarn
No abstract text is available yet for this article.
June 15, 2017: Haematologica
https://www.readbyqxmd.com/read/28619847/targeted-activation-of-the-shp-1-pp2a-signalling-axis-elicits-apoptosis-of-chronic-lymphocytic-leukemia-cells
#6
Elena Tibaldi, Mario Angelo Pagano, Federica Frezzato, Valentina Trimarco, Monica Facco, Giuseppe Zagotto, Giovanni Ribaudo, Valeria Pavan, Luciana Bordin, Andrea Visentin, Francesca Zonta, Gianpietro Semenzato, Anna Maria Brunati, Livio Trentin
The Src Family Kinase (SFK) Lyn is a key factor in the dysregulation of survival and apoptotic pathways of malignant B cells in chronic lymphocytic leukemia. One of the effects of Lyn's action is the spatial and functional segregation of the tyrosine phosphatase SHP-1 into two pools, one beneath the plasma membrane in an active state promoting pro-survival signals, the other in the cytosol in an inhibited conformation and unable to counter the elevated level of cytosolic tyrosine phosphorylation. We herein show that SHP-1 activity can be elicited directly by nintedanib, an agent also known as a triple angiokinase inhibitor, circumventing the phospho-S591-dependent inhibition of the phosphatase, leading to the dephosphorylation of pro-apoptotic players such as procaspase-8 and the serine/threonine phosphatase 2A, eventually triggering apoptosis...
June 15, 2017: Haematologica
https://www.readbyqxmd.com/read/28619846/acute-lymphoblastic-leukemia-cells-create-a-leukemic-niche-without-affecting-the-cxcr4-cxcl12-axis
#7
Bob de Rooij, Roel Polak, Lieke C J van den Berk, Femke Stalpers, Rob Pieters, Monique L den Boer
No abstract text is available yet for this article.
June 15, 2017: Haematologica
https://www.readbyqxmd.com/read/28619845/the-prohibitin-binding-compound-fluorizoline-induces-apoptosis-in-chronic-lymphocytic-leukemia-cells-through-the-upregulation-of-noxa-and-synergizes-with-ibrutinib-aicar-or-venetoclax
#8
Ana M Cosialls, Helena Pomares, Daniel Iglesias-Serret, José Saura-Esteller, Sonia Núñez-Vázquez, Diana M González-Gironès, Esmeralda de la Banda, Sara Preciado, Fernando Albericio, Rodolfo Lavilla, Gabriel Pons, Eva M González-Barca, Joan Gil
Fluorizoline is a new synthetic molecule that induces apoptosis by selectively targeting prohibitins. In this study, the pro-apoptotic effect of fluorizoline was assessed in 34 primary samples from patients with chronic lymphocytic leukemia. Fluorizoline induced apoptosis in chronic lymphocytic leukemia cells at concentrations in the low micromolar range. All primary samples were sensitive to fluorizoline irrespectively of patients' clinical or genetic features, whereas normal T lymphocytes were less sensitive...
June 15, 2017: Haematologica
https://www.readbyqxmd.com/read/28596283/combined-targeting-of-stat3-and-stat5-a-novel-approach-to-overcome-drug-resistance-in-chronic-myeloid-leukemia
#9
Karoline V Gleixner, Mathias Schneeweiss, Gregor Eisenwort, Daniela Berger, Harald Herrmann, Katharina Blatt, Georg Greiner, Konstantin Byrgazov, Gregor Hoermann, Marina Konopleva, Islam Waliul, Abbarna A Cumaraswamy, Patrick T Gunning, Hiroshi Maeda, Richard Moriggl, Michael Deininger, Thomas Lion, Michael Andreeff, Peter Valent
In chronic myeloid leukemia, resistance against BCR-ABL1 tyrosine kinase inhibitors can develop because of BCR-ABL1 mutations, activation of additional pro-oncogenic pathways, and stem cell resistance. Drug combinations covering a broad range of targets may overcome resistance. CDDO-Me is a drug that inhibits the survival of leukemic cells by targeting different pro-survival molecules, including STAT3. We found that CDDO-Me inhibits proliferation and survival of tyrosine kinase inhibitor-resistant BCR-ABL1+ cell lines and primary leukemic cells, including cells harboring BCR-ABL1T315I or T315I+ compound mutations...
June 8, 2017: Haematologica
https://www.readbyqxmd.com/read/28596282/chlorambucil-plus-rituximab-as-front-line-therapy-for-elderly-and-or-unfit-chronic-lymphocytic-leukemia-patients-correlation-with-biologically-based-risk-stratification
#10
Luca Laurenti, Idanna Innocenti, Francesco Autore, Stefania Ciolli, Francesca Romana Mauro, Donato Mannina, Giovanni Del Poeta, Giovanni D'Arena, Massimo Massaia, Marta Coscia, Sandro Molica, Gabriele Pozzato, Dimitar G Efremov, Barbara Vannata, Roberto Marasca, Piero Galieni, Antonio Cuneo, Sonia Orlando, Alfonso Piciocchi, Riccardo Boncompagni, Donatella Vincelli, Anna Marina Liberati, Filomena Russo, Robin Foa'
No abstract text is available yet for this article.
June 8, 2017: Haematologica
https://www.readbyqxmd.com/read/28596281/hemoglobin-concentration-total-hemoglobin-mass-and-plasma-volume-in-patients-implications-for-anemia
#11
James M Otto, James O M Plumb, Eleri Clissold, Shriya Kumar, Denis J Wakeham, Walter Schmidt, Michael P W Grocott, Toby Richards, Hugh Montgomery
In practice, clinicians generally consider anemia (circulating hemoglobin concentration < 120 g.l-1 in non-pregnant females and < 130 g.l-1 in males) as due to impaired hemoglobin synthesis or increased erythrocyte loss or destruction. Rarely is a rise in plasma volume relative to circulating total hemoglobin mass considered as a cause. But does this matter? We explored this issue in patients, using the optimized carbon-monoxide rebreathing method to measure hemoglobin concentration and thereby calculate plasma volume in healthy volunteers, surgical patients, and those with inflammatory bowel disease, chronic liver disease or heart failure...
June 8, 2017: Haematologica
https://www.readbyqxmd.com/read/28596280/extracellular-vesicles-of-bone-marrow-stromal-cells-rescue-chronic-lymphocytic-leukemia-b-cells-from-apoptosis-enhance-their-migration-and-induce-gene-expression-modifications
#12
Emerence Crompot, Michael Van Damme, Karlien Pieters, Marjorie Vermeersch, David Perez-Morga, Philippe Mineur, Marie Maerevoet, Nathalie Meuleman, Dominique Bron, Laurence Lagneaux, Basile Stamatopoulos
Interactions between chronic lymphocytic leukemia B-cells and the bone marrow microenvironment play a major function in the physiopathology of chronic lymphocytic leukemia. Extracellular vesicles, which are composed of exosomes and microparticles, play an important role in cell communication. However, little is known about their role in chronic lymphocytic leukemia/microenvironment interactions. In the present study, extracellular vesicles purified by ultracentrifugation from bone marrow mesenchymal stromal cell cultures were added to chronic lymphocytic leukemia B-cells...
June 8, 2017: Haematologica
https://www.readbyqxmd.com/read/28596279/feasibility-study-of-online-streamed-yoga-for-symptom-management-in-patients-with-myeloproliferative-neoplasms
#13
Jennifer Huberty, Ryan Eckert, Krisstina Gowin, Jules Mitchell, Amylou C Dueck, Brenda F Ginos, Linda Larkey, Ruben Mesa
No abstract text is available yet for this article.
June 8, 2017: Haematologica
https://www.readbyqxmd.com/read/28596278/hla-drb1-07-01-hla-dqa1-02-01-hla-dqb1-02-02-haplotype-is-associated-with-a-high-risk-of-asparaginase-hypersensitivity-in-acute-lymphoblastic-leukemia
#14
Nóra Kutszegi, Xiaoqin Yang, András Gézsi, Géza Schermann, Dániel J Erdélyi, Ágnes F Semsei, Krisztina M Gábor, Judit C Sági, Gábor T Kovács, András Falus, Hongyun Zhang, Csaba Szalai
Hypersensitivity reactions are the most frequent dose-limiting adverse reactions to Escherichia coli-derived asparaginase in pediatric acute lymphoblastic leukemia patients. The aim of the present study was to identify associations between sequence-based Human Leukocyte Antigen Class II region alleles and asparaginase hypersensitivity in a Hungarian acute lymphoblastic leukemia population. Four-digit typing of HLA-DRB1 and HLA-DQB1 loci was performed in 359 pediatric acute lymphoblastic leukemia patients by using next-generation sequencing method...
June 8, 2017: Haematologica
https://www.readbyqxmd.com/read/28572165/long-term-impact-of-joint-bleeds-in-von-willebrand-disease-a-nested-case-control-study
#15
Karin P M van Galen, Piet de Kleijn, Wouter Foppen, Jeroen Eikenboom, Karina Meijer, Roger E G Schutgens, Kathelijn Fischer, Marjon H Cnossen, Joke de Meris, Karin Fijnvandraat, Johanna G van der Bom, Britta A P Laros-van Gorkom, Frank W G Leebeek, Evelien P Mauser-Bunschoten
Patients with severe von Willebrand Disease may develop arthropathy after joint bleeds. Limited information is available on its prevalence and severity. We aimed to assess the occurrence and severity of arthropathy in VWD and its impact on daily life. Von Willebrand Disease patients with and without verified joint bleeds were matched for age, gender and Factor VIII level or Von Willebrand Factor activity in a nested case-control study within the Willebrand in the Netherlands study. Assessments included the Hemophilia Joint Health Score (0-124), Pettersson score (0-13 per joint X-ray), Hemophilia Activity List score (0-100), joint pain (Visual Analog Scale 0-10) and Impact on Participation and Autonomy questionnaire (0-20)...
June 1, 2017: Haematologica
https://www.readbyqxmd.com/read/28572164/risk-of-cardiovascular-events-and-pulmonary-hypertension-following-splenectomy-a-danish-population-based-cohort-study-from-1996-2012
#16
Marianne Rørholt, Waleed Ghanima, Dora Körmendiné Farkas, Mette Nørgaard
Splenectomised patients are at increased risk of cardiovascular events, but it remains unclear whether this is due to lack of the spleen or due to the underlying disease leading to splenectomy. We aimed to assess the risk of myocardial infarction, pulmonary hypertension, and stroke following splenectomy. We identified patients splenectomised in Denmark during 1996-2012. We constructed two comparison cohorts: an age- and sex-matched general population cohort and a disease-matched cohort based on the splenectomy-related underlying disease...
June 1, 2017: Haematologica
https://www.readbyqxmd.com/read/28572163/incidence-of-second-primary-malignancies-and-related-mortality-in-imatinib-treated-chronic-myeloid-leukemia-patients
#17
Gabriele Gugliotta, Fausto Castagnetti, Massimo Breccia, Francesco Albano, Alessandra Iurlo, Tamara Intermesoli, Elisabetta Abruzzese, Luciano Levato, Mariella D'Adda, Patrizia Pregno, Francesco Cavazzini, Fabio Stagno, Bruno Martino, Gaetano La Barba, Federica Sorà, Mario Tiribelli, Catia Bigazzi, Gianni Binotto, Massimiliano Bonifacio, Clementina Caracciolo, Simona Soverini, Robin Foà, Michele Cavo, Giovanni Martinelli, Fabrizio Pane, Giuseppe Saglio, Michele Baccarani, Gianantonio Rosti
The majority of patients with chronic myeloid leukemia are successfully managed with life-long treatment with tyrosine-kinase inhibitors. In patients in chronic phase, other malignancies are among the most common causes of death, raising concerns on the relationship between these deaths and the off-target effects of tyrosine-kinase inhibitors. We analyzed the incidence of second primary malignancies, and related mortality, in 514 chronic myeloid leukemia patients enrolled in clinical trials with imatinib first-line...
June 1, 2017: Haematologica
https://www.readbyqxmd.com/read/28572162/crispr-cas9-induced-t-11-19-mll-enl-translocations-initiate-leukemia-in-human-hematopoietic-progenitor-cells-in-vivo
#18
Jana Reimer, Sabine Knoess, Maurice Labuhn, Emmanuelle M Charpentier, Gudrun Göhring, Brigitte Schlegelberger, Jan-Henning Klusmann, Dirk Heckl
Chromosomal translocations generating oncogenic fusion proteins are causative for most pediatric leukemias and frequently affect the MLL/KMT2A gene. In vivo modeling of bona fide chromosomal translocations in human hematopoietic stem and progenitor cells (HSPCs) is challenging but essential to determine their actual leukemogenic potential. We therefore developed an advanced lentiviral CRISPR-Cas9 vector that efficiently transduced human CD34+-HSPCs and induced the t(11;19)/MLL-ENL translocation. Leveraging this system we could demonstrate that HSPCs harboring the translocation showed only a transient clonal growth advantage in vitro...
June 1, 2017: Haematologica
https://www.readbyqxmd.com/read/28572161/ultrasensitive-detection-of-acute-myeloid-leukemia-minimal-residual-disease-using-single-molecule-molecular-inversion-probes
#19
Adam Waalkes, Kelsi Penewit, Brent L Wood, David Wu, Stephen J Salipante
The identification of minimal residual disease is the primary diagnostic finding which predicts relapse in patients treated for acute myeloid leukemia. Ultrasensitive detection of minimal residual disease would enable better patient risk stratification and could open opportunities for early therapeutic intervention. Here we apply single molecule molecular inversion probe capture, a technology combining multiplexed targeted sequencing with error correction schemes based on molecular barcoding, to detect mutations identifying minimal residual disease with ultrasensitive and quantitative precision...
June 1, 2017: Haematologica
https://www.readbyqxmd.com/read/28554945/genetic-background-and-evolution-of-relapses-in-aggressive-b-cell-lymphomas
#20
Darius Juskevicius, Stephan Dirnhofer, Alexandar Tzankov
Relapses of aggressive B-cell lymphomas pose a higher risk to the affected patients due to potential treatment resistance and usually more aggressive tumor growth. Recent advances, such as targeting Bruton tyrosine kinase showed promising results in small number of cases, however treatment for the majority of patients remains challenging and outcomes are generally poor. Recently, a number of studies were published, which utilized state-of-the-art genomic technologies in an attempt to better understand tumor genome evolution during relapse and identify relapse-specific genetic alterations...
May 29, 2017: Haematologica
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