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John Koreth, Haesook T Kim, Paulina B Lange, Samuel J Poryanda, Carol G Reynolds, Sharmila Chamling Rai, Philippe Armand, Corey S Cutler, Vincent T Ho, Brett Glotzbecker, Rushdia Yusuf, Sarah Nikiforow, Yi-Bin Chen, Bimalangshu Dey, Malgorzata McMasters, Jerome Ritz, Bruce R Blazar, Robert J Soiffer, Joseph H Antin, Edwin P Alyea
A prior phase I/II trial of bortezomib/tacrolimus/methotrexate prophylaxis after HLA-mismatched reduced intensity conditioning allogeneic hematopoietic stem cell transplantation documented low acute graft versus host disease incidence, with promising overall and progression-free survival. We performed an open-label 3-arm 1:1:1 phase II randomized-controlled-trial comparing grade II-IV acute graft versus host disease between conventional tacrolimus/methotrexate (A) versus bortezomib/tacrolimus/methotrexate (B); and versus bortezomib/sirolimus/tacrolimus (C), in reduced intensity conditioning allogeneic transplantation recipients lacking HLA-matched related donors...
January 11, 2018: Haematologica
Claudia Dürr, Bola S Hanna, Angela Schulz, Fabienne Lucas, Manuela Zucknick, Axel Benner, Andrew Clear, Sibylle Ohl, Selcen Öztürk, Thorsten Zenz, Stephan Stilgenbauer, Min Li-Weber, Peter H Krammer, John G Gribben, Peter Lichter, Martina Seiffert
Chronic lymphocytic leukemia is a malignancy of mature B cells that strongly depend on microenvironmental factors and their deprivation has been identified as promising treatment approach for this incurable disease. Cytokine array screening of 247 chronic lymphocytic leukemia serum samples revealed elevated levels of TNF receptor-1 which were associated with poor clinical outcome. We detected a microenvironment-induced expression of TNF receptor-1 in chronic lymphocytic leukemia cells in vitro and aberrantly high expression of this receptor in proliferation centers of patients' lymph nodes...
January 11, 2018: Haematologica
Aniththa Thivakaran, Lacramiora Botezatu, Judith M Hönes, Judith Schütte, Lothar Vassen, Yahya S Al-Matary, Pradeep Patnana, Amos Zeller, Michael Heuser, Felicitas Thol, Razif Gabdoulline, Nadine Olberding, Daria Frank, Marina Suslo, Renata Köster, Klaus Lennartz, Andre Görgens, Bernd Giebel, Bertram Opalka, Ulrich Dührsen, Cyrus Khandanpour
Differentiation of haematopoietic stem cells is regulated by a concert of different transcription factors. Disturbed transcription factors function can be the basis of (pre)malignancies such as myelodysplastic syndrome or acute myeloid leukaemia. Growth factor independence 1b is a repressing transcription factor regulating quiescence of hematopoietic stem cellss and differentiation of erythrocytes and platelets. Here, we show that low expression of Growth factor independence 1b in blast cells is associated with an inferior prognosis of myelodysplastic syndrome and acute myeloid leukaemia patients...
January 11, 2018: Haematologica
Daniela Belloni, Silvia Heltai, Maurilio Ponzoni, Antonello Villa, Barbara Vergani, Lorenza Pecciarini, Magda Marcatti, Stefania Girlanda, Giovanni Tonon, Fabio Ciceri, Federico Caligaris-Cappio, Marina Ferrarini, Elisabetta Ferrero
Multiple myeloma develops primarily inside the bone marrow microenvironment, that confers pro-survival signals and drug resistance. 3D cultures that reproduce multiple myeloma-bone marrow interactions are needed to fully investigate multiple myeloma pathogenesis and response to drugs. To this purpose, we exploited the 3D Rotary Cell Culture System bioreactor technology for myeloma-bone marrow co-cultures in gelatin scaffolds. The model was validated with myeloma cell lines that, as assessed by histochemical and electron-microscopic analyses, engaged contacts with stromal cells and endothelial cells...
January 11, 2018: Haematologica
Nikolett Wohner, Vincent Muczynski, Amel Mohamadi, Paulette Legendre, Gabriel Aymé, Olivier D Christophe, Peter J Lenting, Cécile V Denis, Caterina Casari
Previously, we identified LDL-receptor related protein-1 on macrophages to mediate shear stress-dependent clearance of von Willebrand factor. In control experiments, however, we observed that von Willebrand factor also binds to macrophages independently of this receptor under static conditions, suggesting the existence of additional clearance-receptors. In search for such receptors, we focused on the macrophage-specific scavenger-receptor SR-AI. Von Willebrand factor displays efficient binding to SR-AI (half-max binding 14+/-5 nM)...
January 11, 2018: Haematologica
Olga K Weinberg, Christopher J Gibson, Traci M Blonquist, Donna Neuberg, Olga Pozdnyakova, Frank Kuo, Benjamin L Ebert, Robert P Hasserjian
Despite improvements in our understanding of the molecular basis of acute myeloid leukemia, the association between genetic mutations with morphologic dysplasia remains unclear. In this study, we evaluated and scored dysplasia in bone marrow specimens from 168 patients with de novo acute myeloid leukemia; none of these patients had 2016 WHO Classification-defined cytogenetic abnormalities. We then performed targeted sequencing of diagnostic bone marrow aspirates for recurrent mutations associated with myeloid malignancies...
January 11, 2018: Haematologica
Thibaud Lefebvre, Niloofar Reihani, Raed Daher, Thierry Billette de Villemeur, Nadia Belmatoug, Christian Rose, Yves Colin-Aronovicz, Hervé Puy, Caroline Le Van Kim, Mélanie Franco, Zoubida Karim
Gaucher disease is an inherited deficiency of glucocerebrosidase leading to accumulation of glucosylceramide in tissues such as the spleen, liver, and bone marrow. The resulting lipid-laden macrophages lead to the appearance of Gaucher cells. Anemia associated with an unexplained hyperferritinemia is a frequent finding in Gaucher disease, but whether this pathogenesis is related to an iron metabolism disorder has remained unclear. To investigate this issue, we explored the iron status of a large cohort of 90 type I Gaucher disease patients, including 66 patients treated with enzyme replacement therapy...
January 5, 2018: Haematologica
Meng-Meng Ji, Yao-Hui Huang, Jin-Yan Huang, Zhao-Fu Wang, Di Fu, Han Liu, Feng Liu, Christophe Leboeuf, Li Wang, Jing Ye, Yi-Ming Lu, Anne Janin, Shu Cheng, Wei-Li Zhao
Due to heterogeneous morphological and immunophenotypic features, approximately 50% of peripheral T-cell lymphomas are unclassifiable and categorized as peripheral T-cell lymphomas, not otherwise specified, presenting aggressive disease course and poor clinical outcome. Identification of actionable biomarkers is urgently needed to develop better therapeutic strategies. Epigenetic alterations play a crucial role in tumor progression. Histone modifications, particularly methylation and acetylation, are generally involved in chromatin state regulation...
January 5, 2018: Haematologica
Richa Manwani, Darren Foard, Shameem Mahmood, Sajitha Sachchithanantham, Thirusha Lane, Cristina Quarta, Taryn Youngstein, Tamer Rezk, Helen J Lachmann, Julian D Gillmore, Marianna Fontana, Carol Whelan, Philip N Hawkins, Ashutosh D Wechalekar
No abstract text is available yet for this article.
January 5, 2018: Haematologica
Marina Wierz, Sandrine Pierson, Nora Chouha, Laurent Désaubry, Jean-Hugues François, Guy Berchem, Jerome Paggetti, Etienne Moussay
No abstract text is available yet for this article.
January 5, 2018: Haematologica
Janneke I Loomans, Marieke J H A Kruip, Manuel Carcao, Shannon Jackson, Alice S van Velzen, Marjolein Peters, Elena Santagostino, Helen Platokouki, Erik Beckers, Jan Voorberg, Johanna G van der Bom, Karin Fijnvandraat
Desmopressin increases endogenous factor VIII levels in hemophilia A. Large inter-individual variation in the response to desmopressin is observed. Patients with a lower baseline factor VIII activity tend to show a reduced response. Therefore, desmopressin is less frequently used in moderate hemophilia A patients (baseline factor VIII activity 1-5 international units/deciliter), even though factor VIII levels may rise substantially in some of them. We aim to describe the response to desmopressin in moderate hemophilia A patients and to identify predictors...
January 5, 2018: Haematologica
Esther Heideveld, Lea A Hampton-O'Neil, Stephen J Cross, Floris P J van Alphen, Maartje van den Biggelaar, Ashley M Toye, Emile van den Akker
The classical central macrophage found in erythroblastic islands plays an important role in erythroblast differentiation, proliferation and enucleation in the bone marrow. Convenient human in vitro models to facilitate the study of erythroid-macrophage interactions are desired. Recently, we demonstrated that cultured monocytes/macrophages enhance in vitro erythropoiesis by supporting hematopoietic stem cell survival. Here, we describe that these specific macrophages also support erythropoiesis. Human monocytes cultured in serum-free media supplemented with stem cell factor, erythropoietin, lipids and dexamethasone differentiate towards macrophages expressing CD16, CD163, CD169, CD206, CXCR4 and the phagocytic TAM-receptor family...
December 28, 2017: Haematologica
Matthew S Zabriskie, Orlando Antelope, Anupam R Verma, Lauren R Draper, Christopher A Eide, Anthony D Pomicter, Thai Hoa Tran, Brian J Druker, Jeffrey W Tyner, Rodney R Miles, James M Graham, Jae-Yeon Hwang, Katherine E Varley, Reha M Toydemir, Michael W Deininger, Elizabeth A Raetz, Thomas O'Hare
No abstract text is available yet for this article.
December 28, 2017: Haematologica
Niklas Landberg, Sofia von Palffy, Maria Askmyr, Henrik Lilljebjörn, Carl Sandén, Marianne Rissler, Satu Mustjoki, Henrik Hjorth-Hansen, Johan Richter, Helena Ågerstam, Marcus Järås, Thoas Fioretos
Tyrosine kinase inhibitors are highly effective for treatment of chronic myeloid leukemia, but very few patients are cured. Major drawbacks with tyrosine kinase inhibitors are their low efficacy in eradicating the leukemic stem cells responsible for disease maintenance and relapse upon drug cessation. Here, we performed RNA-sequencing of flow-sorted primitive (CD34+CD38low) and progenitor (CD34+CD38+) chronic phase chronic myeloid leukemia cells and identified transcriptional upregulation of 32 cell surface molecules relative to corresponding normal bone marrow cells...
December 28, 2017: Haematologica
Ronald S Go, Herbert C Heien, Lindsey R Sangaralingham, Elizabeth B Habermann, Nilay D Shah
No abstract text is available yet for this article.
December 21, 2017: Haematologica
Nicolas Vallet, Flore Sicre de Fontbrune, Michaël Loschi, Deborah Desmier, Alban Villate, Fiorenza Barraco, Patrice Chevallier, Louis Terriou, Ibrahim Yakoub-Agha, Annalisa Ruggeri, Mohamad Mohty, Natacha Maillard, Pierre-Simon Rohrlich, Patrice Ceballos, Steéphanie Nguyen, Xavier Poiré, Gaëlle Guillerm, Reza Tabrizi, Jonathan Farhi, Raynier Devillier, Marie-Thérèse Rubio, Gérard Socié, Régis Peffault de Latour
No abstract text is available yet for this article.
December 21, 2017: Haematologica
Roberta Bottega, Elena Nicchia, Enrico Cappelli, Silvia Ravera, Daniela De Rocco, Michela Faleschini, Fabio Corsolini, Filomena Pierri, Michaela Calvillo, Giovanna Russo, Gabriella Casazza, Ugo Ramenghi, Piero Farruggia, Carlo Dufour, Anna Savoia
Fanconi anemia is a rare disease characterized by congenital malformations, aplastic anemia, and predisposition to cancer. Despite the consolidated role of the Fanconi anemia proteins in DNA repair, their involvement in mitochondrial function is emerging. The purpose of this work was to assess whether the mitochondrial phenotype, independent of genomic integrity, could correlate with patient's phenotype. We evaluated mitochondrial and clinical features of eleven affected individuals homozygous or compound heterozygous for p...
December 21, 2017: Haematologica
Florence Pasquier, Caroline Marty, Thomas Balligand, Frédérique Verdier, Sarah Grosjean, Vitalina Gryshkova, Hana Raslova, Stefan N Constantinescu, Nicole Casadevall, William Vainchenker, Christine Bellanné-Chantelot, Isabelle Plo
Primary Familial and Congenital Polycythemia is characterized by erythropoietin hypersensitivity of erythroid progenitors due to germline nonsense or frameshift mutations in the erythropoietin receptor gene. All mutations already described lead to the truncation of the C-terminal receptor sequence that contains negative regulatory domains. Their removal is presented as sufficient to cause the erythropoietin hypersensitivity phenotype. Here, we provide evidence for a new mechanism whereby the presence of novel sequences generated by frameshift mutations are required for the phenotype rather than just extensive truncation resulting from nonsense mutations...
December 21, 2017: Haematologica
Panagiotis Baliakas, Mattias Mattsson, Anastasia Hadzidimitriou, Eva Minga, Andreas Agathangelidis, Lesley-Ann Sutton, Lydia Scarfo, Zadie Davis, Xiao-Jie Yan, Karla Plevova, Yorick Sandberg, Fie J Vojdeman, Tatiana Tzenou, Charles C Chu, Silvio Veronese, Larry Mansouri, Karin E Smedby, Véronique Giudicelli, Florence Nguyen-Khac, Panagiotis Panagiotidis, Gunnar Juliusson, Achilles Anagnostopoulos, Marie-Paule Lefranc, Livio Trentin, Mark Catherwood, Marco Montillo, Carsten U Niemann, Anton W Langerak, Sarka Pospisilova, Niki Stavroyianni, Nicholas Chiorazzi, David Oscier, Diane F Jelinek, Tait Shanafelt, Nikos Darzentas, Chrysoula Belessi, Frederic Davi, Paolo Ghia, Richard Rosenquist, Kostas Stamatopoulos
No abstract text is available yet for this article.
December 21, 2017: Haematologica
Xiao Fang, Feiyang Shen, Christophe Lechauve, Peng Xu, Guowei Zhao, Jacobi Itkow, Fan Wu, Yaying Hou, Xiaohui Wu, Lingling Yu, Huiqing Xiu, Mengli Wang, Ruiling Zhang, Fangfang Wang, Yanqing Zhang, Daxin Wang, Mitchell J Weiss, Duonan Yu
The microRNAs miR-144 and -451 are encoded by a bicistronic gene that is strongly induced during red blood cell formation (erythropoiesis). Ablation of the miR-144/451 gene in mice causes mild anemia under baseline conditions. Here we show that miR-144/451-/- erythroblasts exhibit increased apoptosis during recovery from acute anemia. Mechanistically, miR-144/451 depletion increases the expression of the miR-451 target mRNA Cab39, which encodes a cofactor for the serine-threonine kinase LKB1. During erythropoietic stress, miR-144/451-/- erythroblasts exhibit abnormally increased Cab39 protein, which activates LKB1 and its downstream AMPK/mTOR effector pathway...
December 21, 2017: Haematologica
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