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https://www.readbyqxmd.com/read/28814386/the-role-of-anthracycline-and-comprehensive-geriatric-assessment-for-elderly-patients-with-diffuse-large-b-cell-lymphoma
#1
Richard J Lin, Madhusmita Behera, Catherine S Diefenbach, Christopher R Flowers
No abstract text is available yet for this article.
August 16, 2017: Blood
https://www.readbyqxmd.com/read/28811306/replication-and-validation-of-genetic-polymorphisms-associated-with-survival-after-allogeneic-blood-or-marrow-transplant
#2
Ezgi Karaesmen, Abbas A Rizvi, Leah Preus, Philip L McCarthy, Marcelo C Pasquini, Kenan Onel, Xiaochun Zhu, Stephen Spellman, Christopher A Haiman, Daniel O Stram, Loreall Pooler, Xin Sheng, Qianqian Zhu, Li Yan, Qian Liu, Qiang Hu, Amy Webb, Guy Brock, Alyssa I Clay-Gilmour, Sebastiano Battaglia, David Tritchler, Song Liu, Theresa Hahn, Lara E Sucheston-Campbell
Multiple candidate gene association studies of non-HLA single nucleotide polymorphisms (SNPs) and outcomes after blood or marrow transplant (BMT) have been conducted. We identified 70 publications reporting 45 SNPs in 36 genes significantly associated with disease-related mortality, progression-free survival, transplant-related mortality and/or overall survival after BMT. Replication and validation of these SNP associations were performed using DISCOVeRY-BMT, a well-powered genome-wide association study consisting of two cohorts, totaling 2,883 BMT recipients with AML, ALL or MDS and their HLA-matched unrelated donors, treated from 2000-2011 and reported to the CIBMTR...
August 15, 2017: Blood
https://www.readbyqxmd.com/read/28811305/red-blood-cells-in-thrombosis
#3
James R Byrnes, Alisa S Wolberg
Red blood cells (RBCs) have historically been considered passive bystanders in thrombosis. However, clinical and epidemiological studies have associated quantitative and qualitative abnormalities in RBCs, including altered hematocrit, sickle cell disease, thalassemia, hemolytic anemias, and malaria, with both arterial and venous thrombosis. A growing body of mechanistic studies suggests RBCs can promote thrombus formation and enhance thrombus stability. These findings suggest RBCs may contribute to thrombosis pathophysiology and reveal potential strategies for therapeutically targeting RBCs to reduce thrombosis...
August 15, 2017: Blood
https://www.readbyqxmd.com/read/28811304/selectin-catch-bonds-mechanotransduce-integrin-activation-and-neutrophil-arrest-on-inflamed-endothelium-under-shear-flow
#4
Vasilios A Morikis, Shannon Chase, Ted Wun, Elliot L Chaikof, John L Magnani, Scott I Simon
E-selectin extends from the plasma membrane of inflamed endothelium and serves to capture leukocytes from flowing blood via long-lived catch-bonds that support slow leukocyte rolling under shear stress. Its ligands are glycosylated with the tetrasaccharide sialyl Lewis(x) (sLe(x)), which contributes to bond affinity and specificity. E-selectin mediated rolling transmits signals into neutrophils that triggers activation of high-affinity β2-integrins necessary for transition to shear resistant adhesion and transendothelial migration...
August 15, 2017: Blood
https://www.readbyqxmd.com/read/28807983/cancer-associated-pathways-and-biomarkers-of-venous-thrombosis
#5
Yohei Hisada, Nigel Mackman
Cancer patients have an increased risk of venous thromboembolism (VTE). In this review, we will summarize common and cancer type-specific pathways of VTE in cancer patients. Increased levels of leukocytes, platelets and tissue factor-positive (TF+) microvesicles are all potential factors that alone or in combination increase cancer-associated thrombosis. Lung and colorectal cancer patients often exhibit leukocytosis. Neutrophils could increase VTE in cancer patients by releasing neutrophil extracellular traps whereas monocytes may express TF...
August 14, 2017: Blood
https://www.readbyqxmd.com/read/28807982/c-ebp%C3%AE-is-required-for-survival-of-ly6c-monocytes
#6
Akihiro Tamura, Hideyo Hirai, Asumi Yokota, Naoka Kamio, Atsushi Sato, Tsukimi Shoji, Takahiro Kashiwagi, Yusuke Torikoshi, Yasuo Miura, Daniel G Tenen, Taira Maekawa
The transcription factor CCAAT/enhancer-binding protein β (C/EBPβ) is highly expressed in monocytes/macrophages. However, its roles in monopoiesis are largely unknown. Here, we investigated the roles of C/EBPβ in monopoiesis. Further subdivision of monocytes revealed that Cebpb mRNA was highly upregulated in Ly6C(-) monocytes in bone marrow. Accordingly, Ly6C(-) monocytes were significantly reduced in Cebpb(-/-) mice. Bone marrow chimera experiments and Mx1-Cre-mediated deletion of Cebpb revealed the cell-intrinsic and monocyte-specific requirement for C/EBPβ in monopoiesis...
August 14, 2017: Blood
https://www.readbyqxmd.com/read/28807981/delineation-of-the-timing-of-second-line-therapy-post-autologous-stem-cell-transplant-in-patients-with-al-amyloidosis
#7
Yi L Hwa, Rahma Warsame, Morie A Gertz, Francis K Buadi, Martha Q Lacy, Shaji K Kumar, David Dingli, Steve R Zeldenrust, Nelson Leung, Suzanne R Hayman, Prashant Kapoor, Wilson I Gonsalves, Taxiarchis V Kourelis, Stephen Russell, Ronald S Go, Miriam A Hobbs, Amie L Fonder, S Vincent Rajkumar, Angela Dispenzieri
Among patients with immunoglobulin light chain (AL) amyloidosis, there is little consensus on when reinstitution of chemotherapy should occur. We conducted a retrospective study to evaluate the patterns of relapse or progression (R/P) and the timing of re-initiating therapy among 235 patients initially treated with ASCT at Mayo Clinic. The median time from ASCT to second-line therapy was 24.3 months. At the time of restarting therapy, median dFLC was 9.9 mg/dL (42% of diagnosis value); 32% had a dFLC< 5mg/dL; and 63% met criteria for organ R/P...
August 14, 2017: Blood
https://www.readbyqxmd.com/read/28807980/cd177-modulates-human-neutrophil-migration-through-activation-mediated-integrin-and-chemoreceptor-regulation
#8
Ming Bai, Ricardo Grieshaber-Bouyer, Junxia Wang, Angela B Schmider, Zachary S Wilson, Liling Zeng, Olha Halyabar, Matthew D Godin, Hung N Nguyen, Anaïs Levescot, Pierre Cunin, Craig T Lefort, Roy J Soberman, Peter A Nigrovic
CD177 is a GPI-anchored protein expressed by a variable proportion of human neutrophils that mediates surface expression of the anti-neutrophil cytoplasmic antibody (ANCA) antigen proteinase 3. CD177 associates with β2 integrins and recognizes PECAM-1, suggesting a role in neutrophil migration. However, CD177(pos) neutrophils exhibit no clear migratory advantage in vivo, despite interruption of transendothelial migration by in vitro CD177 ligation. We sought to understand this paradox. Using a PECAM-1-independent transwell system, we found that CD177(pos) and CD177(neg) neutrophils migrated comparably...
August 14, 2017: Blood
https://www.readbyqxmd.com/read/28801451/adult-high-grade-b-cell-lymphoma-with-burkitt-lymphoma-signature-genomic-features-and-potential-therapeutic-targets
#9
Alyssa Bouska, Chengfeng Bi, Waseem Lone, Weiwei Zhang, Ambreen Kedwaii, Tayla Heavican, Cynthia M Lachel, Jiayu Yu, Roberto Ferro, Nanees Eldorghamy, Timothy C Greiner, Julie Vose, Dennis D Weisenburger, Randy D Gascoyne, Andreas Rosenwald, German Ott, Elias Campo, Lisa M Rimsza, Elaine S Jaffe, Rita M Braziel, Reiner Siebert, Rodney R Miles, Sandeep Dave, Anupama Reddy, Jan Delabie, Louis M Staudt, Joo Y Song, Timothy W McKeithan, Kai Fu, Michael Green, Wing C Chan, Javeed Iqbal
The adult high-grade B-cell lymphomas sharing molecular features with Burkitt lymphoma (BL) are highly aggressive lymphomas with poor clinical outcome. High-resolution structural and functional genomic analysis of adult Burkitt lymphoma (BL) and high-grade B-cell lymphoma with BL gene-signature (adult-mBL), revealed the MYC-ARF-p53 axis as the primary deregulated pathway. Adult-mBL had either unique or more frequent genomic aberrations (del13q14, del17p, gain8q24 and gain18q21) compared with pediatric-mBL, but shared commonly mutated genes...
August 11, 2017: Blood
https://www.readbyqxmd.com/read/28801450/genomic-analysis-of-hairy-cell-leukemia-identifies-novel-recurrent-genetic-alterations
#10
Benjamin H Durham, Bartlomiej Getta, Sascha Dietrich, Justin Taylor, Helen Won, James M Bogenberger, Sasinya Scott, Eunhee Kim, Young Rock Chung, Stephen S Chung, Jennifer Hüllein, Tatjana Walther, Lu Wang, Sydney X Lu, Christopher C Oakes, Raoul Tibes, Torsten Haferlach, Barry S Taylor, Martin S Tallman, Michael F Berger, Jae H Park, Thorsten Zenz, Omar Abdel-Wahab
Classical hairy cell leukemia (cHCL) is characterized by a near 100% frequency of the BRAFV600E mutation while ~30% of variant HCL (vHCL) have MAP2K1 mutations. However, recurrent genetic alterations cooperating with BRAFV600E or MAP2K1 mutations in HCL, as well as those in MAP2K1- wildtype vHCL, are not well defined. We therefore performed deep targeted mutational and copy number analysis of cHCL (n=53) and vHCL (n=8). The most common genetic alteration in cHCL outside of BRAFV600E was heterozygous loss of chromosome 7q, the minimally deleted region of which targeted wildtype BRAF, subdividing cHCL into those hemizygous versus heterozygous for the BRAFV600E mutation...
August 11, 2017: Blood
https://www.readbyqxmd.com/read/28801449/engraftment-and-in-vivo-proliferation-advantage-of-gene-corrected-mobilized-cd34-cells-from-fanconi-anemia-patients
#11
Paula Río, Susana Navarro, Guillermo Guenechea, Rebeca Sánchez-Domínguez, Maria Luisa Lamana, Rosa Yañez, Jose A Casado, Parinda A Mehta, Maria Roser Pujol, Jordi Surrallés, Sabine Charrier, Anne Galy, José C Segovia, Cristina Díaz de Heredia, Julián Sevilla, Juan Bueren
Previous Fanconi anemia (FA) gene therapy studies have failed to demonstrate engraftment of gene corrected hematopoietic stem and progenitor cells (HSPC) from FA patients, either after autologous transplantation or infusion into immunodeficient mice. In this study we demonstrate that a validated short transduction protocol of G-CSF plus plerixafor-mobilized CD34(+) cells from FA-A patients with a therapeutic FANCA-lentiviral vector corrects the phenotype of in vitro cultured hematopoietic progenitor cells. Transplantation of transduced FA CD34(+) cells into immunodeficient mice resulted in reproducible engraftment of myeloid, lymphoid and CD34(+) cells...
August 11, 2017: Blood
https://www.readbyqxmd.com/read/28801448/long-term-results-of-a-phase-ii-study-of-rituximab-and-bendamustine-for-mucosa-associated-lymphoid-tissue-lymphoma
#12
Antonio Salar, Eva Domingo-Domenech, Carlos Panizo, Concepción Nicolás, Joan Bargay, Ana Muntañola, Miguel Canales, José Luis Bello, Juan Manuel Sancho, José Francisco Tomás, María José Rodríguez, Javier Peñalver, Carlos Grande, José Javier Sánchez-Blanco, Luis Palomera, Reyes Arranz, Eulogio Conde, Mar García, Juan Fernando García, Dolores Caballero, Carlos Montalbán
No abstract text is available yet for this article.
August 11, 2017: Blood
https://www.readbyqxmd.com/read/28798157/pregnancy-outcomes-in-inherited-bone-marrow-failure-syndromes
#13
John M Gansner, Maureen M Achebe, Kathryn J Gray, Revital Yefidoff-Freedman, Elena Labovitis, Aric Parnes, Jean M Connors, Nathan T Connell, Marie N Discenza, Robert I Handin, Nancy Berliner, Akiko Shimamura, Elizabeth S Ginsburg, Nicole A Smith
No abstract text is available yet for this article.
August 10, 2017: Blood
https://www.readbyqxmd.com/read/28794072/ruxolitinib-versus-best-available-therapy-for-et-intolerant-or-resistant-to-hydroxycarbamide-in-a-randomized-trial
#14
Claire N Harrison, Adam J Mead, Anesh Panchal, Sonia Fox, Christina Yap, Emmanouela Gbandi, Aimee Houlton, Samah Alimam, Joanne Ewing, Marion Wood, Frederick Chen, Jason Coppell, Nicki Panoskaltsis, Steven Knapper, Sahra Ali, Angela Hamblin, Ruben Scherber, Amylou C Dueck, Nicholas C P Cross, Ruben Mesa, Mary Frances McMullin
Treatments for high-risk essential thrombocythemia (ET) address thrombocytosis, disease-related symptoms, as well as risks of thrombosis, hemorrhage, transformation to myelofibrosis and leukemia. Patients resistant/intolerant to hydroxycarbamide (HC) have a poor outlook. MAJIC (ISRCTN61925716) is a randomized phase II trial of ruxolitinib (JAK1/2 inhibitor) vs Best Available Therapy (BAT) in ET and polycythemia vera (PV) patients resistant or intolerant to HC. Here findings of MAJIC-ET are reported, where the modified intention-to-treat population included 58 & 52 patients randomized to receive ruxolitinib or BAT respectively...
August 9, 2017: Blood
https://www.readbyqxmd.com/read/28794071/a-multi-institutional-outcomes-analysis-of-patients-with-relapsed-or-refractory-dlbcl-treated-with-ibrutinib
#15
Allison M Winter, Daniel J Landsburg, Anthony R Mato, Krista Isaac, Francisco J Hernandez-Ilizaliturri, Nishitha Reddy, Stephen Smith, Mazyar Shadman, Mitchell R Smith, Paolo Caimi, Deepa Jagadeesh, Brian T Hill
No abstract text is available yet for this article.
August 9, 2017: Blood
https://www.readbyqxmd.com/read/28794070/integrin-%C3%AE-iib%C3%AE-3-outside-in-signaling
#16
Tom N Durrant, Marion T van den Bosch, Ingeborg Hers
Integrin αIIbβ3 is a highly abundant heterodimeric platelet receptor that can transmit information bidirectionally across the plasma membrane, and plays a critical role in hemostasis and thrombosis. Upon platelet activation, inside-out signaling pathways increase the affinity of αIIbβ3 for fibrinogen and other ligands. Ligand binding and integrin clustering subsequently stimulate outside-in signaling, which initiates and amplifies a range of cellular events driving essential platelet processes such as spreading, thrombus consolidation and clot retraction...
August 9, 2017: Blood
https://www.readbyqxmd.com/read/28794069/phase-i-study-of-the-anti-cd22-immunotoxin-moxetumomab-pasudotox-for-childhood-acute-lymphoblastic-leukemia
#17
Alan S Wayne, Nirali N Shah, Deepa Bhojwani, Lewis B Silverman, James A Whitlock, Maryalice Stetler-Stevenson, Weili Sun, Meina Liang, Jie Yang, Robert J Kreitman, Mark C Lanasa, Ira Pastan
Novel therapies are needed to overcome chemotherapy resistance for children with relapsed/refractory acute lymphoblastic leukemia (ALL). Moxetumomab pasudotox is a recombinant anti-CD22 immunotoxin. A multicenter, phase I study was conducted to determine the maximum tolerated cumulative dose (MTCD) and evaluate safety, activity, pharmacokinetics, and immunogenicity of moxetumomab pasudotox in children, adolescents, and young adults with ALL (n=55). Moxetumomab pasudotox was administered as a 30-minute intravenous infusion at doses of 5 to 50 µg/kg every other day (QOD) for six (Cohorts A and B) or 10 (Cohort C) doses, on 21-day cycles...
August 9, 2017: Blood
https://www.readbyqxmd.com/read/28790107/runx1-is-required-for-oncogenic-myb-and-myc-enhancer-activity-in-t-cell-acute-lymphoblastic-leukemia
#18
AHyun Choi, Anuradha Illendula, John A Pulikkan, Justine E Roderick, Jessica Tesell, Jun Yu, Nicole Hermance, Lihua Julie Zhu, Lucio H Castilla, John H Bushweller, Michelle A Kelliher
The gene encoding the RUNX1 transcription factor is mutated in a subset of T cell acute lymphoblastic leukemia (T-ALL) patients and RUNX1 mutations are associated with a poor prognosis. These mutations cluster in the DNA binding Runt domain, are thought to represent loss-of-function mutations, indicating that RUNX1 suppresses T cell transformation. RUNX1 has been proposed to have tumor suppressor roles in TLX1/3 transformed human T-ALL cell lines and NOTCH1 T-ALL mouse models. Yet retroviral insertional mutagenesis screens identify RUNX genes as collaborating oncogenes in MYC-driven leukemia mouse models...
August 8, 2017: Blood
https://www.readbyqxmd.com/read/28790106/kit-signaling-is-dispensable-for-human-mast-cell-progenitor-development
#19
Joakim S Dahlin, Maria Ekoff, Jennine Grootens, Liza Löf, Rose-Marie Amini, Hans Hagberg, Johanna S Ungerstedt, Ulla Olsson-Strömberg, Gunnar Nilsson
Human hematopoietic progenitors are generally assumed to require stem cell factor (SCF) and KIT signaling during differentiation for the formation of mast cells. Imatinib treatment, which inhibits KIT signaling, depletes mast cells in vivo. Furthermore, the absence of SCF or imatinib treatment prevents progenitors from developing into mast cells in vitro. However, these observations do not mean that mast cell progenitors require SCF and KIT signaling throughout differentiation. Here, we demonstrate that circulating mast cell progenitors are present in patients undergoing imatinib treatment...
August 8, 2017: Blood
https://www.readbyqxmd.com/read/28790105/value-of-cytogenetic-abnormalities-in-adults-with-ph-negative-b-cell-precursor-acute-lymphoblastic-leukemia
#20
Marina Lafage-Pochitaloff, Laurence Baranger, Mathilde Hunault, Wendy Cuccuini, Christine Lefebvre, Audrey Bidet, Isabelle Tigaud, Virginie Eclache, Eric Delabesse, Chrystèle Bilhou-Nabéra, Christine Terré, Elise Chapiro, Nathalie Gachard, Marie-Joelle Mozziconacci, Geneviève Ameye, Sarah Porter, Nathalie Grardel, Marie C Béné, Yves Chalandon, Carlos Graux, Françoise Huguet, Véronique Lhéritier, Norbert Ifrah, Hervé Dombret
Multiple cytogenetic subgroups have been described in adult Philadelphia chromosome (Ph)-negative B-cell precursor (BCP) acute lymphoblastic leukemia (ALL), often comprising small numbers of patients. In this study, we aimed to reassess the prognostic value of cytogenetic abnormalities in a large series of 617 adult patients with Ph-negative BCP-ALL (median age, 38 years), treated in the intensified GRAALL-2003/2005 trials. Combined data from karyotype, DNA index, FISH and/or PCR screening for relevant abnormalities were centrally reviewed and were informative in 542 cases (88%), allowing classification in ten exclusive primary cytogenetic subgroups and in secondary subgroups including complex and monosomal karyotypes...
August 8, 2017: Blood
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