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Haematologica

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https://www.readbyqxmd.com/read/28082345/gfi1b-controls-integrin-signaling-dependent-cytoskeleton-dynamics-and-organization-in-megakaryocytes
#1
Hugues Beauchemin, Peiman Shooshtarizadeh, Charles Vadnais, Lothar Vassen, Yves D Pastore, Tarik Möröy
Mutations in GFI1B are associated with inherited bleeding disorders called GFI1B-related thrombocytopenias. We show here that mice with a megakaryocyte-specific Gfi1b deletion exhibit a macrothrombocytopenic phenotype along a megakaryocytic dysplasia reminiscent of GFI1B-related thrombocytopenias. Gfi1b deficiency increases megakaryocyte proliferation and affects their ploidy, but also abrogates their responsiveness towards integrin signaling and their ability to spread and reorganize their cytoskeleton. Gfi1b-null megakaryocytes are also unable to form proplatelets, a process independent of integrin signaling...
January 12, 2017: Haematologica
https://www.readbyqxmd.com/read/28082344/is-immunotherapy-here-to-stay-in-multiple-myeloma
#2
Paula Rodriguez-Otero, Bruno Paiva, Monika Engelhardt, Felipe Prósper, Jesus F San Miguel
Immune escape and impaired immune surveillance have been identified as emerging hallmarks of cancer (1). Multiple Myeloma represents a genuine example of disrupted immune surveillance characterized by: impaired antibody production, deregulation of the T and NK cell compartment, disruption of antigen presentation machinery, upregulation of inhibitory surface ligands and recruitment of immunosuppressive cells. Although the potential value of immunotherapeutic interventions had a clear antecedent in the graft-versus-myeloma effect induced by allogeneic SCT and donor-lymphocyte infusions, it is only until recently that this field has faced a real revolution...
January 12, 2017: Haematologica
https://www.readbyqxmd.com/read/28082343/integrative-clinicopathological-and-molecular-analyses-of-angioimmunoblastic-t-cell-lymphoma-and-other-nodal-lymphomas-of-follicular-helper-t-cell-origin
#3
Maria Pamela Dobay, Francois Lemonnier, Edoardo Missiaglia, Christian Bastard, David Vallois, Jean-Philippe Jais, Laurianne Scourzic, Aurélie Dupuy, Virginie Fataccioli, Anais Pujals, Marie Parrens, Fabien Le Bras, Thérèse Rousset, Jean-Michel Picquenot, Nadine Martin, Corinne Haioun, Richard Delarue, Olivier A Bernard, Mauro Delorenzi, Laurence de Leval, Philippe Gaulard
No abstract text is available yet for this article.
January 12, 2017: Haematologica
https://www.readbyqxmd.com/read/28082342/second-line-rituximab-lenalidomide-and-bendamustine-r2b-in-mantle-cell-lymphoma-a-phase-2-clinical-trial-of-the-fondazione-italiana-linfomi
#4
Francesco Zaja, Simone Ferrero, Caterina Stelitano, Angela Ferrari, Flavia Salvi, Annalisa Arcari, Gerardo Musuraca, Barbara Botto, Michele Spina, Claudia Cellini, Caterina Patti, Anna M Liberati, Claudia Minotto, Stefano A Pileri, Manuela Ceccarelli, Stefano Volpetti, Antonella Ferranti, Daniela Drandi, Elisa Montechiarello, Marco Ladetto, James Carmichael, Renato Fanin
No abstract text is available yet for this article.
January 12, 2017: Haematologica
https://www.readbyqxmd.com/read/28082341/the-transcription-factor-gata1-regulates-nbeal2-expression-through-a-long-distance-enhancer
#5
Anouck Wijgaerts, Christine Wittevrongel, Chantal Thys, Timothy Devos, Kathelijne Peerlinck, Marloes R Tijssen, Chris Van Geet, Kathleen Freson
Gray platelet syndrome is named after the gray appearance of platelets due to absence of alpha(α)-granules. It is caused by recessive mutations in NBEAL2, resulting in macrothrombocytopenia and myelofibrosis. Though using the term gray platelets for GATA1 deficiency has been debated, a reduced number of α-granules has been described for macrothrombocytopenia due to GATA1 mutations. We compared platelet size and number of α-granules for two NBEAL2 and two GATA1 deficient patients and found reduced numbers of α-granules for all, with the defect being more pronounced for NBEAL2 deficiency...
January 12, 2017: Haematologica
https://www.readbyqxmd.com/read/28082340/long-term-relapse-free-survival-in-a-phase-2-study-of-blinatumomab-for-the-treatment-of-patients-with-minimal-residual-disease-in-b-lineage-acute-lymphoblastic-leukemia
#6
Nicola Gökbuget, Gerhard Zugmaier, Matthias Klinger, Peter Kufer, Matthias Stelljes, Andreas Viardot, Heinz A Horst, Svenja Neumann, Monika Brüggemann, Oliver G Ottmann, Thomas Burmeister, Dorothea Wessiepe, Max S Topp, Ralf Bargou
No abstract text is available yet for this article.
January 12, 2017: Haematologica
https://www.readbyqxmd.com/read/28082339/bcr-abl-translocation-as-a-favorable-prognostic-factor-in-elderly-acute-lymphoblastic-leukemia-patients-in-potent-tyrosine-kinase-era
#7
Ja Min Byun, Youngil Koh, Dong-Yeop Shin, Inho Kim, Sung-Soo Yoon, Jeong-Ok Lee, Soo-Mee Bang, Ki Hwan Kim, Sung-Hoon Jung, Won Sik Lee, Yong Park, Jun Ho Jang, Jae Joon Han, Ho-Young Yhim, Dae Sik Kim, Yoo Jin Lee, Hyewon Lee, Yun-Suk Choi, Seok Lee
No abstract text is available yet for this article.
January 12, 2017: Haematologica
https://www.readbyqxmd.com/read/28057744/hematopoiesis-in-patients-with-mature-b-cell-malignancies-is-deregulated-even-in-patients-with-undetectable-bone-marrow-involvement
#8
Bokang Calvin Lenyeletse Maswabi, Jan Molinsky, Filipp Savvulidi, Tomas Zikmund, Dana Prukova, Diana Tuskova, Magdalena Klanova, Petra Vockova, Lucie Lateckova, Ludek Sefc, Jan Zivny, Marek Trneny, Pavel Klener
No abstract text is available yet for this article.
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28057743/il21r-expressing-cd14-cd16-monocytes-expand-in-multiple-myeloma-patients-leading-to-increased-osteoclasts
#9
Marina Bolzoni, Domenica Ronchetti, Paola Storti, Gaetano Donofrio, Valentina Marchica, Federica Costa, Luca Agnelli, Denise Toscani, Rosanna Vescovini, Katia Todoerti, Sabrina Bonomini, Gabriella Sammarelli, Andrea Vecchi, Daniela Guasco, Fabrizio Accardi, Benedetta Dalla Palma, Barbara Gamberi, Carlo Ferrari, Antonino Neri, Franco Aversa, Nicola Giuliani
Bone marrow monocytes are primarily committed to osteoclast formation. It is, however, unknown whether potential primary alterations are specifically present in bone marrow monocytes of multiple myeloma patients, smoldering myeloma or monoclonal gammopathy of uncertain significance. Herein, we analyzed the immunophenotypic and transcriptional profiles of bone marrow CD14+ monocytes in a cohort of patients with different types of monoclonal gammopathies to identify alterations involved in myeloma-enhanced osteoclastogenesis...
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28057742/dual-role-of-il-21-in-megakaryopoiesis-and-platelet-homeostasis
#10
Salima Benbarche, Catherine Strassel, Catherine Angénieux, Léa Mallo, Monique Freund, Christian Gachet, François Lanza, Henri de la Salle
Gene profiling studies have indicated that in vitro differentiated human megakaryocytes express the receptor for IL-21 (IL-21R), an immunostimulatory cytokine associated with inflammatory disorders and currently under evaluation in cancer therapy. The aim of this study was to investigate whether IL-21 modulates megakaryopoiesis. We first checked the expression of IL-21 receptor on human bone marrow and in vitro differentiated megakaryocytes. Then, we investigated the effect of IL-21 on the in vitro differentiation of human blood CD34+ progenitors into megakaryocytes...
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28057741/factor-viii-v-c-domain-swaps-reveal-discrete-c-domain-roles-in-factor-viii-function-and-intracellular-trafficking
#11
Eduard H T M Ebberink, Eveline A M Bouwens, Esther Bloem, Mariëtte Boon-Spijker, Maartje Van den Biggelaar, Jan Voorberg, Alexander B Meijer, Koen Mertens
Factor VIII C-domains are believed to contain specific function in co-factor activity and in interaction with von Willebrand factor. We have previously shown that factor VIII is co-targeted with von Willebrand factor to the Weibel-Palade bodies in blood outgrowth endothelial cells, even when factor VIII carries mutations in the light chain that are associated with defective von Willebrand factor binding. In this study we furthermore addressed the contribution of individual factor VIII C-domains in intracellular targeting, von Willebrand factor binding and co-factor activity by factor VIII/V C-domain swapping...
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28057740/dasatinib-and-allogeneic-stem-cell-transplantation-enable-sustained-response-in-an-elderly-patient-with-rcsd1-abl1-positive-acute-lymphoblastic-leukemia
#12
Miriam Frech, Lutz B Jehn, Kathleen Stabla, Stephan Mielke, Björn Steffen, Hermann Einsele, Stephan K Metzelder, Andreas Neubauer
No abstract text is available yet for this article.
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28057739/aberrant-let7a-hmga2-signaling-activity-with-unique-clinical-phenotype-in-jak2-mutated-myeloproliferative-neoplasms
#13
Chih-Cheng Chen, Jie-Yu You, Jrhau Lung, Cih-En Huang, Yi-Yang Chen, Yu-Wei Leu, Hsing-Ying Ho, Chian-Pei Li, Chang-Hsien Lu, Kuan-Der Lee, Chia-Chen Hsu, Jyh-Pyng Gau
High mobility group AT-hook 2 (HMGA2) is an architectural transcriptional factor that is negatively regulated by Let-7 microRNA through binding to its 3-untranslated region (3-UTR). Transgenic mice expressing HMGA2 with a truncation of its 3-UTR has been shown to exhibit a myeloproliferative phenotype. To decipher the Let-7-HMGA2 axis in myeloproliferative neoplasms (MPN), we employed an in vitro model supplemented with clinical correlation. Ba/F3 cells with inducible JAK2V617F expression (Ton.JAK2.V617F cells) showed up-regulation of HMGA2 with concurrent let-7a repression...
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28057738/a-population-of-hematopoietic-stem-cells-derives-from-gata4-expressing-progenitors-located-in-the-placenta-and-lateral-mesoderm-of-mice
#14
Ana Cañete, Rita Carmona, Laura Ariza, Maria Jose Sanchez, Anabel Rojas, Ramon Muñoz-Chápuli
GATA transcription factors are expressed in mesoderm and endoderm during development. GATA1-3, but not GATA4, are critically involved in hematopoiesis. An enhancer (G2) of the mouse Gata4 gene directs its expression throughout the lateral mesoderm and the allantois, beginning at E7.5, becoming restricted to the septum transversum by E10.5, and disappearing by midgestation. We have studied the developmental fate of the G2-Gata4 cell lineage using a G2-Gata4Cre;R26REYFP mouse line. We found a substantial number of YFP+ hematopoietic cells of lymphoid, myeloid and erythroid lineages in embryos...
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28057737/deep-and-sustained-response-after-venetoclax-therapy-in-a-patient-with-very-advanced-refractory-myeloma-with-translocation-t-11-14
#15
Cyrille Touzeau, Steven Le Gouill, Béatrice Mahé, Jean-Samuel Boudreault, Thomas Gastinne, Nicolas Blin, Hélène Caillon, Christelle Dousset, Martine Amiot, Philippe Moreau
No abstract text is available yet for this article.
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28057736/acute-myeloid-leukemias-with-ring-sideroblasts-show-a-unique-molecular-signature-straddling-secondary-acute-myeloid-leukemia-and-de-novo-acute-myeloid-leukemia
#16
Pedro Martin-Cabrera, Sabine Jeromin, Karolína Peglorová, Claudia Haferlach, Wolfgang Kern, Torsten Haferlach
No abstract text is available yet for this article.
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28057735/increased-age-associated-mortality-risk-in-hla-mismatched-hematopoietic-stem-cell-transplantation
#17
Daniel Fürst, Dietger Niederwieser, Donald Bunjes, Eva M Wagner, Martin Gramatzki, Gerald Wulf, Carlheinz R Müller, Christine Neuchel, Chrysanthi Tsamadou, Hubert Schrezenmeier, Joannis Mytilineos
We investigated a possible interaction between age-associated risk and HLA-mismatch associated risk on prognosis in different age categories of recipients of unrelated hematopoietic stem cell transplants (HSCT) (n=3019). Patients over 55 years of age transplanted with 8/10 donors showed a mortality risk of 2.27 (CI 1.70-3.03, p<0.001) and 3.48 (CI 2.49-4.86, p<0.001) when compared to 10/10 matched patients in the same age group and to 10/10 matched patients aged 18-35 years, respectively. Compared to 10/10 matched transplantations within each age category, the HR for 8/10 matched transplantation was 1...
January 5, 2017: Haematologica
https://www.readbyqxmd.com/read/28034993/lenalidomide-combined-with-intensive-chemotherapy-in-acute-myeloid-leukemia-and-higher-risk-myelodysplastic-syndrome-with-5q-deletion-results-of-a-phase-ii-study-by-the-groupe-francophone-des-myelodysplasies
#18
Lionel Ades, Thomas Prebet, Aspasia Stamatoullas, Christian Recher, Romain Guieze, Emmanuel Raffoux, Krimo Bouabdallah, Mathilde Hunault, Eric Wattel, Laure Stalnikiewicz, Andrea Toma, Herve' Dombret, Nobert Vey, Marie Sebert, Claude Gardin, Cendrine Chaffaut, Sylvie Chevret, Pierre Fenaux
Patients with acute myeloblastic leukemia or higher risk myelodysplastic syndromes with 5q deletion (generally within complex karyotype) respond poorly to intensive chemotherapy and have very poor survival. In this population, we evaluated escalating doses of lenalidomide combined with IC in a phase II study (NCT00885508) Treatment consisted of daunorubicin (45 mg/m2/d1-3 in cohort 1, escalated to 60mg/m2/1-3 in cohorts2 and 3) combined with AraC (200mg/m2/ d1-7) and lenalidomide (10mg/d1-21 in cohorts1 and 2, escalated to 25mg/d1-21 in cohort 3)...
December 29, 2016: Haematologica
https://www.readbyqxmd.com/read/28034992/plerixafor-and-g-csf-combination-mobilizes-hematopoietic-stem-and-progenitors-cells-with-a-distinct-transcriptional-profile-and-a-reduced-in-vivo-homing-capacity-compared-to-plerixafor-alone
#19
Maria Rosa Lidonnici, Annamaria Aprile, Marta Claudia Frittoli, Giacomo Mandelli, Ylenia Paleari, Antonello Spinelli, Bernhard Gentner, Matilde Zambelli, Cristina Parisi, Laura Bellio, Elena Cassinerio, Laura Zanaboni, Maria Domenica Cappellini, Fabio Ciceri, Sarah Marktel, Giuliana Ferrari
No abstract text is available yet for this article.
December 29, 2016: Haematologica
https://www.readbyqxmd.com/read/28034991/impact-of-flt3-itd-diversity-on-response-to-induction-chemotherapy-in-patients-with-acute-myeloid-leukemia
#20
Mike Fischer, Ulf Schnetzke, Bärbel Spies-Weisshart, Mario Walther, Maximilian Fleischmann, Inken Hilgendorf, Andreas Hochhaus, Sebastian Scholl
No abstract text is available yet for this article.
December 29, 2016: Haematologica
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