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https://www.readbyqxmd.com/read/29789357/reactivation-of-%C3%AE-globin-in-adult-%C3%AE-yac-mice-after-ex-vivo-and-in-vivo-hematopoietic-stem-cell-genome-editing
#1
Chang Li, Nikoletta Psatha, Pavel Sova, Sucheol Gil, Hongjie Wang, Jiho Kim, Chandana Kulkarni, Cristina Valensisi, R David Hawkins, George Stamatoyannopoulos, André Lieber
Disorders involving β-globin gene mutations, mainly β-thalassemia and sickle cell disease, represent a major target for hematopoietic stem/progenitor cell (HSPC) gene therapy. This includes CRISPR/Cas9-mediated genome editing approaches in adult CD34+ cells aimed toward the re-activation of fetal γ-globin expression in red blood cells. Because models involving erythroid differentiation of CD34+ cells have limitations in assessing γ-globin re-activation, we focused on human β-globin locus transgenic (β-YAC) mice...
May 22, 2018: Blood
https://www.readbyqxmd.com/read/29789356/risk-adapted-treatment-of-acute-promyelocytic-leukemia-results-from-international-consortium-for-childhood-apl
#2
Anna Maria Testi, Andrea Pession, Daniela Diverio, David Grimwade, Brenda Gibson, Amilcar Cardoso de Azevedo, Lorena Moran, Guy Leverger, Sarah Elitzur, Henrik Hasle, Jutte van der Werff Ten Bosch, Owen Smith, Marisa De Rosa, Alfonso Piciocchi, Francesco Lo Coco, Robin Foà, Franco Locatelli, Gertjan J L Kaspers
Pediatric acute promyelocytic leukemia (APL), a rare childhood neoplasm, can be cured with all-trans retinoic acid (ATRA) and anthracycline. However, most published trials to date have employed high cumulative doses of anthracyclines. Here, we report the outcome of patients with newly diagnosed APL enrolled into the International Consortium for Childhood APL (ICC-APL-01) trial, which reduced anthracycline exposure but extended that of ATRA. The study recruited 258 children/adolescents with molecularly/cytogenetically-proven APL...
May 22, 2018: Blood
https://www.readbyqxmd.com/read/29784643/the-presence-of-large-focal-lesions-is-a-strong-independent-prognostic-factor-in-multiple-myeloma
#3
Leo Rasche, Edgardo J Angtuaco, Terri L Alpe, Grant H Gershner, James E McDonald, Rohan S Samant, Manoj Kumar, Rudy Van Hemert, Joshua Epstein, Shayu Deshpande, Ruslana Tytarenko, Shmuel Yaccoby, Jens Hillengass, Sharmilan Thanendrarajan, Carolina Schinke, Frits van Rhee, Maurizio Zangari, Brian A Walker, Bart Barlogie, Gareth J Morgan, Faith E Davies, Niels Weinhold
Spatial intra-tumor heterogeneity is frequently seen in Multiple Myeloma (MM) and poses a significant challenge for risk classifiers, which rely on tumor samples from the iliac crest. As biopsy based assessment of multiple skeletal sites is difficult, alternative strategies for risk stratification are required. Recently, the size of focal lesions (FL) was shown to be a surrogate marker for spatial heterogeneity, suggesting that data from medical imaging could be used to improve risk stratification approaches...
May 21, 2018: Blood
https://www.readbyqxmd.com/read/29784642/identification-of-key-lipids-critical-for-platelet-activation-by-comprehensive-analysis-of-the-platelet-lipidome
#4
Bing Peng, Sascha Geue, Cristina Coman, Patrick Münzer, Dominik Kopczynski, Canan Has, Nils Hoffmann, Mailin-Christin Manke, Florian Lang, Albert Sickmann, Meinrad Gawaz, Oliver Borst, Robert Ahrends
Platelet integrity and function critically depend on lipid composition. However, the lipid inventory in platelets was hitherto not quantified. Here, we examined the lipidome of murine platelets using lipid-category tailored protocols on a quantitative lipidomics platform. We could show that the platelet lipidome comprises almost 400 lipid species and covers a concentration range of seven orders of magnitude. A systematic comparison of the lipidomics network in resting and activated murine platelets, validated in human platelets, revealed that less than 20% of the platelet lipidome is changed upon activation, involving mainly lipids containing arachidonic acid...
May 21, 2018: Blood
https://www.readbyqxmd.com/read/29784641/intrinsic-apoptosis-circumvents-the-functional-decline-of-circulating-platelets-but-does-not-cause-the-storage-lesion
#5
Irina Pleines, Marion Lebois, Pradnya Gangatirkar, Amanda E Au, Rachael M Lane, Katya J Henley, Maria Kauppi, Jason Corbin, Ping Cannon, Jonathan Bernardini, Imala Alwis, Kate E Jarman, Sarah Ellis, Donald Metcalf, Shaun P Jackson, Simone M Schoenwaelder, Benjamin T Kile, Emma C Josefsson
The circulating life span of blood platelets is regulated by the pro-survival protein BCL-XL. It restrains the activity of BAK and BAX, the essential pro-death mediators of intrinsic apoptosis. Disabling the platelet intrinsic apoptotic pathway in mice by deleting BAK and BAX results in a doubling of platelet life span and concomitant thrombocytosis. Apoptotic platelets expose phosphatidylserine (PS) via a mechanism that is distinct from that driven by classical agonists. Whether there is any role for apoptotic PS in platelet function in vivo, however, is unclear...
May 21, 2018: Blood
https://www.readbyqxmd.com/read/29784640/hypoxia-downregulates-protein-s-expression
#6
Vijaya S Pilli, Arani Datta, Sadaf Afreen, Donna Catalano, Gyongyi Szabo, Rinku Majumder
No abstract text is available yet for this article.
May 21, 2018: Blood
https://www.readbyqxmd.com/read/29784639/tyrosine-kinase-inhibitor-induced-defects-in-dna-repair-sensitize-flt3-itd-positive-leukemia-cells-to-parp1-inhibitors
#7
Silvia Maifrede, Margaret Nieborowska-Skorska, Katherine Sullivan, Yashodhara Dasgupta, Paulina Podszywalow-Bartnicka, Bac Viet Le, Martyna Solecka, Zhaorui Lian, Elizaveta A Belyaeva, Alina Nersesyan, Marcin M Machnicki, Monika Toma, Nicolas Chatain, Malgorzata Rydzanicz, Huaqing Zhao, Jaroslav Jelinek, Katarzyna Piwocka, Tomasz Sliwinski, Tomasz Stoklosa, Rafal Ploski, Thomas Fischer, Stephen M Sykes, Steffen Koschmieder, Lars Bullinger, Peter Valent, Mariusz Wasik, Jian Huang, Tomasz Skorski
Mutations in the FMS-like tyrosine-kinase 3 (FLT3) such as internal tandem duplications (ITD) can be found in up to 23% of patients with acute myeloid leukemia (AML) and confer a poor prognosis. Current treatment options for FLT3(ITD)-positive AMLs include genotoxic therapy and FLT3 inhibitors (FLT3i), which are rarely curative. PARP1 inhibitors (PARP1i) have been successfully applied to induce synthetic lethality in tumors harboring BRCA1/2 mutations and displaying homologous recombination (HR) deficiency...
May 21, 2018: Blood
https://www.readbyqxmd.com/read/29784638/syndromic-congenital-myelofibrosis-associated-with-a-loss-of-function-variant-in-rbsn
#8
Pilar L Magoulas, Oleg A Shchelochkov, Matthew N Bainbridge, Shay Ben-Shachar, Svetlana Yatsenko, Lorraine Potocki, Richard Alan Lewis, Charles Searby, Andrea N Marcogliese, M Tarek Elghetany, Gladys Zapata, Paula Patricia Hernández, Manasi Gadkari, Derek Einhaus, Donna M Muzny, Richard A Gibbs, Alison A Bertuch, Daryl A Scott, Silvia Corvera, Luis M Franco
No abstract text is available yet for this article.
May 21, 2018: Blood
https://www.readbyqxmd.com/read/29776907/single-cell-exomes-in-an-index-case-of-amp1q21-multiple-myeloma-reveals-more-diverse-mutanomes-than-the-whole-population
#9
Dean Bryant, Will Tapper, Nicola J Weston-Bell, Arnold Bolomsky, Li Song, Shengtao Xu, Andrew R Collins, Niklas Zojer, Surinder Singh Sahota
No abstract text is available yet for this article.
May 18, 2018: Blood
https://www.readbyqxmd.com/read/29776906/blood-induced-bone-loss-in-murine-hemophilic-arthropathy-is-prevented-by-blocking-the-irhom2-adam17-tnf%C3%AE-pathway
#10
Coline Haxaire, Narine Hakobyan, Tania Pannellini, Camila Carballo, David McIlwain, Tak W Mak, Scott Rodeo, Suchitra Acharya, Daniel Li, Jackie Szymonifka, Xiangqian Song, Sébastien Monette, Alok Srivastava, Jane E Salmon, Carl P Blobel
Hemophilic arthropathy (HA) is a debilitating degenerative joint disease that is a major manifestation of the bleeding disorder Hemophilia A. HA typically begins with hemophilic synovitis (HS) that resembles inflammatory arthritides such as rheumatoid arthritis (RA) and frequently results in bone loss in patients. A major cause of RA is inappropriate release of the pro-inflammatory cytokine tumor necrosis factor α (TNFα) by the TNFα convertase (TACE, also referred to as ADAM17) and its regulator, iRhom2...
May 18, 2018: Blood
https://www.readbyqxmd.com/read/29773572/hemostatic-efficacy-of-pathogen-inactivated-versus-untreated-platelets-a-randomized-controlled-trial
#11
Pieter F van der Meer, Paula F Ypma, Nan van Geloven, Joost A van Hilten, Rinie J van Wordragen-Vlaswinkel, Okke Eissen, Jaap J Zwaginga, MIchael Trus, Erik A M Beckers, Peter Te Boekhorst, Alan Tinmouth, Yulia Lin, Cyrus Hsia, David Lee, Philip J Norris, Raymond P Goodrich, Anneke Brand, Tor Hervig, Nancy M Heddle, Johanna G van der Bom, Jean-Louis H Kerkhoffs
Pathogen inactivation of platelet concentrates reduces the risk of blood-borne infections. However, its effect on platelet function and hemostatic efficacy of transfusion is unclear. We conducted a randomized noninferiority trial comparing the efficacy of pathogen inactivated platelets using riboflavin and ultraviolet B illumination technology (intervention) compared to standard plasma-stored platelets (control) for the prevention of bleeding in patients with hematologic malignancies and thrombocytopenia. The primary outcome parameter was the proportion of transfusion treatment periods in which the patient had grade 2 or higher bleeding as defined by World Health Organization (WHO) criteria...
May 17, 2018: Blood
https://www.readbyqxmd.com/read/29769264/rhoa-g17v-is-sufficient-to-induce-autoimmunity-and-promotes-t-cell-lymphomagenesis-in-mice
#12
Samuel Y Ng, Leon Brown, Kristen Stevenson, Tiffany deSouza, Jon C Aster, Abner Louissaint, David M Weinstock
Patients with angioimmunoblastic T-cell lymphoma (AITL) and other peripheral T-cell lymphomas (PTCL) that harbor features of follicular helper T (TFH) cells have a very poor prognosis. These lymphomas commonly present with paraneoplastic autoimmunity and lymphopenia. RhoA G17V mutation is present in 60% of TFH-like lymphomas but its role in tumorigenesis is poorly understood. We generated transgenic mice that express RhoA G17V under the control of murine CD4 regulatory elements at levels comparable to a heterozygous mutation (tgRhoA mice)...
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29769263/how-i-treat-burkitt-lymphoma-in-children-adolescents-and-young-adults-in-sub-saharan-africa
#13
Satish Gopal, Thomas G Gross
Burkitt lymphoma (BL) is the most common pediatric cancer in sub-Saharan Africa (SSA), and also occurs frequently among adolescents and young adults (AYA), often associated with human immunodeficiency virus (HIV). Treating BL in SSA poses particular challenges. Although highly effective, high-intensity cytotoxic treatments used in resource-rich settings are usually not feasible, and lower-intensity continuous infusion approaches are impractical. In this paper, based on evidence from the region, we review management strategies for SSA focused on diagnosis, use of pre-phase, and definitive treatment...
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29769262/a-new-molecular-assay-and-genomic-complexity-predict-outcome-in-conventional-and-leukemic-non-nodal-mantle-cell-lymphoma
#14
Guillem Clot, Pedro Jares, Eva Giné, Alba Navarro, Cristina Royo, Magda Pinyol, David Martín-Garcia, Santiago Demajo, Blanca Espinet, Antonio Salar, Ana Ferrer, Ana Muntañola, Marta Aymerich, Hilka Rauert-Wunderlich, Elaine S Jaffe, Joseph M Connors, Randy D Gascoyne, Jan Delabie, Armando López-Guillermo, German Ott, George W Wright, Louis M Staudt, Andreas Rosenwald, David W Scott, Lisa M Rimsza, Sílvia Beà, Elías Campo
Mantle cell lymphoma (MCL) is an aggressive B-cell malignancy but some patients have a very indolent evolution. This heterogeneous course is related, in part, to the different biological characteristics of conventional MCL (cMCL) and the distinct subgroup of leukemic non-nodal MCL (nnMCL). Robust criteria to distinguish these MCL subtypes and additional biological parameters that influence their evolution are not well defined. Herein, we describe a novel molecular assay that reliably distinguishes cMCL and nnMCL using blood samples...
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29769261/prognostic-factors-influencing-survival-after-allogeneic-transplantation-for-aml-mds-patients-with-tp53-mutations
#15
Stefan O Ciurea, Abhishek Chilkulwar, Rima M Saliba, Julianne Chen, Gabriela Rondon, Keyur P Patel, Haitham Khogeer, Abdul R Shah, Brion V Randolph, Jorge M Ramos Perez, Uday Popat, Chitra M Hosing, Qaiser Bashir, Rohtesh Mehta, Gheath Al-Atrash, Jin Im, Issa F Khouri, Partow Kebriaei, Richard E Champlin
No abstract text is available yet for this article.
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29769260/bim-regulates-the-survival-and-suppressive-capability-of-cd8-foxp3-regulatory-t-cells-during-murine-gvhd
#16
Kimberle Agle, Benjamin G Vincent, Clint Piper, Ludovic Belle, Vivian Zhou, Warren Shlomchik, Jonathan S Serody, William R Drobyski
CD8+ Foxp3+ T cells (Tregs) are a potent regulatory population whose functional and ontological similarities to CD4+ Fox3+ T cells have not been well delineated. Using an experimental model of graft versus host disease (GVHD), we observed that CD8+ Tregs were significantly less potent than CD4+ Tregs for the suppression of GVHD. To define the mechanistic basis for this observation, we examined the T cell repertoire and the transcriptional profile of in vivo-derived CD4+ and CD8+ Tregs that emerged early during this disease...
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29769259/novel-therapeutics-for-hemophilia-and-other-bleeding-disorders
#17
Michael U Callaghan, Robert Sidonio, Steven W Pipe
Hemophilia and von Willebrand disease are the most common congenital bleeding disorders. Treatment for these disorders has focused on replacement of the missing coagulation factor to prevent or treat bleeding. New technologies and insights into hemostasis have driven the development of many promising new therapies for hemophilia and von Willebrand disease. Emerging bypass agents including zymogen-like factor IXa and Xa molecules are in development and a bispecific antibody, emicizumab, demonstrated efficacy in a phase III trial in people with hemophilia A and inhibitors...
May 16, 2018: Blood
https://www.readbyqxmd.com/read/29764840/how-we-diagnose-and-treat-venous-thromboembolism-in-sickle-cell-disease
#18
Arun S Shet, Theodore Wun
The incidence of venous thromboembolism (VTE) in adult patients with sickle cell disease (SCD) is high. However, overlapping features between the clinical presentation of VTE and SCD complications and a low index of suspicion for thrombosis can influence patient management decisions. VTE in SCD can therefore present management challenges to the clinical hematologist. Herein, we present three distinct clinical vignettes that are representative of our clinical practice with SCD patients. These vignettes are discussed with specific reference to the hypercoagulable state in SCD patients, recent VTE diagnosis and anticoagulant therapy guidelines from the general population, and evaluation of the risk of bleeding as a result of long term exposure to anticoagulant therapy...
May 15, 2018: Blood
https://www.readbyqxmd.com/read/29764839/lineage-restriction-analyses-in-chip-indicate-myeloid-bias-for-tet2-and-multipotent-stem-cell-origin-for-dnmt3a
#19
Manuel Buscarlet, Sylvie Provost, Yassamin Feroz Zada, Vincent Bourgoin, Luigina Mollica, Marie-Pierre Dubé, Lambert Busque
We analyzed DNA from PMN (granulocytes), CD14+ (monocytes), CD19+ (B-cells) and CD3+ (T-cells) of 107 individuals with clonal hematopoiesis of indeterminate potential (CHIP) to perform lineage restriction analysis of different gene mutations. Individuals were aged 55 to 96 (mean age: 70.0). Three lineage categories were defined: myeloid (PMN±monocytes), myelolympho-B (myeloid and B-cells), multipotent (myeloid, B and T-cells). Six individuals with aberrant patterns were excluded from analysis. Fifty-six had a single DNMT3A mutation, 24 had a single TET2 mutation, 7 had a single mutation in other genes (JAK2, ASXL1, CBL or TP53), and 14 had multiple mutations...
May 15, 2018: Blood
https://www.readbyqxmd.com/read/29764838/a-common-tcn1-loss-of-function-variant-is-associated-with-lower-vitamin-b12-concentration-in-african-americans
#20
Yao Hu, Laura M Raffield, Linda M Polfus, Arden Moscati, Girish Nadkarni, Michael H Preuss, Xue Zhong, Qiang Wei, Stephen S Rich, Yun Li, James G Wilson, Adolfo Correa, Ruth J F Loos, Bingshan Li, Paul L Auer, Alex P Reiner
No abstract text is available yet for this article.
May 15, 2018: Blood
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