journal
https://read.qxmd.com/read/38522092/sars-cov-2-infection-modifies-the-transcriptome-of-the-megakaryocytes-in-the-bone-marrow
#21
JOURNAL ARTICLE
Isabelle Allaeys, Guillaume Lemaire, Mickael Leclercq, Emile Lacasse, Maude Fleury, Isabelle Dubuc, Leslie Gudimard, Florian Puhm, Julia Tilburg, Andrew P Stone, Kellie R Machlus, Arnaud Droit, Louis Flamand, Eric Boilard
Megakaryocytes, integral to platelet production, predominantly reside in the bone marrow and undergo regulated fragmentation within sinusoid vessels to release platelets into the bloodstream. Inflammatory states and infections influence megakaryocyte transcription, potentially affecting platelet functionality. Notably, COVID-19 has been associated with altered platelet transcriptomes. In this study, we investigated the hypothesis that SARS-CoV-2 infection could impact the transcriptome of bone marrow megakaryocytes...
March 24, 2024: Blood Advances
https://read.qxmd.com/read/38513140/pd1-inhibits-pkc%C3%AE-dependent-phosphorylation-of-cytoskeleton-related-proteins-and-immune-synapse-formation
#22
JOURNAL ARTICLE
Daniela Chmiest, Silvia Podavini, Kalliopi Ioannidou, David Vallois, Chantal Décaillet, Montserrat Gonzalez, Manfredo Quadroni, Kevin Blackney, Rebekka Schairer, Laurence L de Leval, Margot Thome
The inhibitory cell surface receptor programmed death 1 (PD1) is a major target for antibody-based cancer immunotherapies. Nevertheless, a substantial number of patients fail to respond to the treatment or experience adverse effects. An improved understanding of intracellular pathways targeted by PD1 is thus needed to develop better predictive and prognostic biomarkers. Here, via unbiased phosphoproteome analysis of primary human T cells, we demonstrate that PD1 triggering inhibited the phosphorylation and physical association with PKC theta (PKCof a variety of cytoskeleton-related proteins...
March 21, 2024: Blood Advances
https://read.qxmd.com/read/38513139/runx1-c-terminal-mutations-impair-blood-cell-differentiation-by-perturbing-specific-enhancer-promoter-networks
#23
JOURNAL ARTICLE
Nathan Daniel Jayne, Zhengyu Liang, Do-Hwan Lim, Poshen Benson Chen, Cristina Diaz, Kei-Ichiro Arimoto, Lingbo Xia, Mengdan Liu, Bing Ren, Xiang-Dong Fu, Dong-Er Zhang
The transcription factor RUNX1 is a master regulator of hematopoiesis and is frequently mutated in myeloid malignancies. Mutations in its runt homology domain (RHD) frequently disrupt DNA binding and result in loss of RUNX1 function. However, it is not clearly understood how other RUNX1 mutations contribute to disease development. Here, we characterize RUNX1 mutations outside of the RHD. Our analysis of patient datasets revealed that mutations within the C-terminus frequently occur in hematopoietic disorders...
March 21, 2024: Blood Advances
https://read.qxmd.com/read/38513135/genomic-profiling-of-mycosis-fungoides-identifies-patients-at-high-risk-of-disease-progression
#24
JOURNAL ARTICLE
Léa Fléchon, Inès Arib, Ankit K Dutta, Lama Hasan Bou Issa, Romanos Sklavenitis-Pistofidis, Remi Tilmont, Chip Stewart, Romain Dubois, Stéphanie Poulain, Marie-Christine Copin, Sahir Javed, Morgane Nudel, Doriane Cavalieri, Guillaume Escure, Nicolas Gower, Paul Chauvet, Nicolas Gazeau, Cynthia Saade, Marietou Binta Thiam, Aïcha Ouelkite-Oumouchal, Silvia Gaggero, Émeline Cailliau, Sarah Faiz, Olivier Carpentier, Nicolas Duployez, Thierry B Idziorek, Laurent Mortier, Martin Figeac, Claude Preudhomme, Bruno Quesnel, Suman Mitra, Franck Morschhauser, Gad Getz, Irene M Ghobrial, Salomon Manier
Mycosis fungoides (MF) is the most prevalent primary cutaneous T-cell lymphoma, with an indolent or aggressive course and poor survival. The pathogenesis of MF remains unclear, and prognostic factors in the early stages are not well-established. Here, we characterized the most recurrent genomic alterations using whole-exome sequencing of 67 samples from 48 patients from Lille University Hospital (France), including 18 sequential samples drawn across stages of the malignancy. Genomic data were analyzed on the Broad Institute's Terra bioinformatics platform...
March 21, 2024: Blood Advances
https://read.qxmd.com/read/38513134/platelet-proteomic-profiling-in-sitosterolemia-suggests-thrombocytopenia-is-driven-by-lipid-disorder-and-not-platelet-aberrations
#25
JOURNAL ARTICLE
Jessica Del Castillo Alferez, Anton T J Tool, Karin van Leeuwen, Floris P J van Alphen, Marion M Brands, Monique H Suijker, Alexander B Meijer, Arie J Hoogendijk, Taco W Kuijpers
Sitosterolemia is a rare autosomal-recessive genetic disorder in which patients develop hypercholesterolemia, and may exhibit abnormal hematologic and/or liver test results. In this disease, dysfunction of either ABCG5 or ABCG8 results in intestinal hyperabsorption of all sterols, including cholesterol and more specifically plant sterols or xenosterols, as well as in the impaired ability to excrete xenosterols into the bile. It remains unknown how and why some patients develop hematologic abnormalities. Only a few unrelated patients with hematologic abnormalities at the time of diagnosis have been reported...
March 21, 2024: Blood Advances
https://read.qxmd.com/read/38513088/mechanisms-of-resistance-to-bispecific-t-cell-engagers-in-multiple-myeloma-and-their-clinical-implications
#26
JOURNAL ARTICLE
Eric Letouzé, Philippe Moreau, Nikhil C Munshi, Mehmet K Samur, Stephane Minvielle, Cyrille Touzeau
Bispecific T cell engagers (TCE) are revolutionizing patient care in multiple myeloma (MM). These monoclonal antibodies, that redirect T cells against cancer cells, are now approved for the treatment of triple-class exposed relapsed refractory multiple myeloma (RRMM). They are currently tested in earlier lines of the disease, including in first line. Yet, primary resistance occurs in about one third of RRMM patients, and most responders eventually develop acquired resistance. Understanding the mechanisms of resistance to bispecific TCE is thus essential to improve immunotherapies in MM...
March 21, 2024: Blood Advances
https://read.qxmd.com/read/38513082/therapy-related-chronic-myelomonocytic-leukemia-does-not-have-the-high-risk-features-of-a-therapy-related-neoplasm
#27
JOURNAL ARTICLE
Alex Bataller, Georgina Gener-Ricos, Emmanuel Almanza, Kelly Sharon Chien, Samuel Urrutia, Alexandre Bazinet, Juan Jose Rodriguez-Sevilla, Danielle Hammond, Koji Sasaki, Koichi Takahashi, Courtney D DiNardo, Farhad Ravandi, Gautam Borthakur, Tapan M Kadia, Rashmi Kanagal-Shamanna, Hagop M Kantarjian, Guillermo Garcia-Manero, Guillermo Montalban-Bravo
Therapy-related myeloid neoplasms (t-MNs) arise after exposure to cytotoxic therapies and are associated with high-risk genetic features and poor outcomes. We analyzed a cohort of patients with therapy-related chronic myelomonocytic leukemia (tCMML; n = 71) and compared its features to that of de novo CMML (dnCMML; n = 461). Median time from cytotoxic therapy to tCMML diagnosis was 6.5 years. Compared with dnCMML, chromosome 7 abnormalities (4% vs. 13%; P = .005), but not complex karyotype (3% vs. 7%; P = ...
March 21, 2024: Blood Advances
https://read.qxmd.com/read/38513079/targeting-neutrophil-extracellular-trap-under-flow-in-patients-with-immune-mediated-thrombotic-thrombocytopenic-purpura
#28
JOURNAL ARTICLE
Noritaka Yada, Quan Zhang, Antionia Bignotti, Sarah H Gralnek, Dennis Sosnovske, Keenan O Hogan, Zhan Ye, Liang Zheng, X Long Zheng
Neutrophil NETosis is a unique form of cell death, characterized by release of decondensed chromatin and anti-microbial contents to the extracellular space, involved in infection, inflammation, and thrombosis. However, the role of NETosis in pathogenesis of immune-mediated thrombotic thrombocytopenic purpura (iTTP) and how a targeted therapy affects the accumulation of neutrophil extracellular traps (NETs) under flow remain to be determined. Flow cytometry demonstrated that the percentage of neutrophils undergoing NETosis in whole blood from iTTP patients on admission is significantly increased with a concurrent decrease in the capacity of inducible NETosis by shigatoxin...
March 21, 2024: Blood Advances
https://read.qxmd.com/read/38507746/cytoreductive-therapy-in-younger-adults-with-polycythemia-vera-a-meta-analysis-of-safety-and-outcomes
#29
JOURNAL ARTICLE
Reem S Chamseddine, Oleksandr Savenkov, Shehroz Tariq Rana, Mohammed Khalid, Richard T Silver, Nicole Kucine, Joseph Michael Scandura, Ghaith Abu-Zeinah
Cytoreductive therapy is not routinely recommended for younger patients with polycythemia vera (PV) due to concern that treatment toxicity may outweigh therapeutic benefits. However, no systematic data supports this approach. To support objective risk/benefit assessment of cytoreductive drugs in PV patients younger than 60 (PV<60), this systematic review and meta-analysis was conducted to evaluate toxicity and disease-related complications in PV<60 treated with interferon alfa (rIFNα) or hydroxyurea (HU)...
March 20, 2024: Blood Advances
https://read.qxmd.com/read/38507742/daratumumab-monotherapy-in-refractory-warm-autoimmune-hemolytic-anemia-and-cold-agglutinin-disease
#30
JOURNAL ARTICLE
Marit Jalink, Chaja F Jacobs, Jahanzaib Khwaja, Dorothea Evers, Coty Bruggeman, Bruno Fattizzo, Marc Michel, Etienne Crickx, Quentin A A Hill, Ulrich Jaeger, Arnon P Kater, Anja B U Mäkelburg, Anouk Breedijk, Peter A W Te Te Boekhorst, Marlijn P A Hoeks, Masja de de Haas, Shirley P D'Sa, Josephine M I M I Vos
Autoimmune hemolytic anemia (AIHA) is a rare autoantibody-mediated disease. For steroid and/or rituximab-refractory AIHA, there is no consensus on optimal treatment. Daratumumab, a monoclonal antibody targeting CD38, could be beneficial by suppression of CD38+ plasmacells and thus autoantibody secretion. In addition, since CD38 is also expressed by activated T-cells, daratumumab may also act via immunomodulatory effects. We evaluated efficacy and safety of daratumumab monotherapy in an international retrospective study including 19 adult patients with heavily pretreated refractory AIHA...
March 20, 2024: Blood Advances
https://read.qxmd.com/read/38507738/in-btk-phosphorylated-y223-in-the-sh3-domain-mirrors-catalytic-activity-but-does-not-influence-biological-function
#31
JOURNAL ARTICLE
Hernando Yesid Estupiñan Velasquez, Thibault Bouderlique, Chenfei He, Anna Berglöf, Andrea Cappelleri, Nicolai Frengen, Rula Zain, Mikael C I Karlsson, Robert Månsson, C I Edvard Smith
Bruton's tyrosine kinase (BTK) is an enzyme needed for B-cell survival and inhibitors have become potent targeted medicines for the treatment of B-cell malignancies. The initial activation event of cytoplasmic protein-tyrosine kinases is the phosphorylation of a conserved regulatory tyrosine in the catalytic domain, which in BTK is represented by tyrosine 551. In addition, the tyrosine 223 (Y223) residue in the SRC homology 3 (SH3) domain has for more than two decades generally been considered necessary for full enzymatic activity...
March 20, 2024: Blood Advances
https://read.qxmd.com/read/38507736/multiomic-profiling-of-human-clonal-hematopoiesis-reveals-genotype-and-cell-specific-inflammatory-pathway-activation
#32
JOURNAL ARTICLE
Jonathan Brett Heimlich, Pawan Bhat, Alyssa Parker, Matthew T Jenkins, Caitlyn Vlasschaert, Jessica Ulloa, Joseph Van Amburg, Chad R Potts, Sydney Olson, Alexander J Silver, Ayesha Ahmad, Brian Sharber, Donovan Brown, Ningning Hu, Peter van Galen, Michael R Savona, Alexander G Bick, Paul Brent Ferrell
Clonal hematopoiesis (CH) is an age-associated phenomenon that increases risk for hematologic malignancy and cardiovascular disease. CH is thought to enhance disease risk through inflammation in the peripheral blood1. Here, we profile peripheral blood gene expression in 66,968 single cells from a cohort of 17 CH patients and 7 controls. Using a novel mitochondrial DNA barcoding approach, we were able to identify and separately compare mutant TET2 and DNMT3A cells to non-mutant counterparts. We discovered the vast majority of mutated cells were in the myeloid compartment...
March 20, 2024: Blood Advances
https://read.qxmd.com/read/38507689/blinatumomab-consolidation-for-adult-b-cell-acute-lymphoblastic-leukemia-in-first-and-second-complete-remission
#33
JOURNAL ARTICLE
Irene Urbino, Etienne Lengliné, Florence Rabian, Marco Cerrano, Rathana Kim, Florian Chevillon, Dario Ferrero, Marie Sébert, Nathalie Dhedin, Raphaël A Itzykson, Lionel Adès, Emmanuel Raffoux, Hervé Dombret, Ernesta Audisio, Emmanuelle Clappier, Nicolas Boissel
No abstract text is available yet for this article.
March 20, 2024: Blood Advances
https://read.qxmd.com/read/38507688/differentiation-syndrome-associated-with-treatment-with-idh2-inhibitor-enasidenib-pooled-analysis-from-clinical-trials
#34
JOURNAL ARTICLE
Pau Montesinos, Amir T Fathi, Stéphane de Botton, Eytan M Stein, Amer M Zeidan, Yue Zhu, Thomas Prebet, Carlos Enrique Vigil, Iryna Bluemmert, Xin Yu, Courtney D DiNardo
Treatment with enasidenib, a selective mutant-IDH2 inhibitor, has been associated with the development of differentiation syndrome (DS) in patients with acute myeloid leukemia (AML). Studies on the incidence and clinical features of DS are limited in this setting, and diagnosis is challenging due to non-specific symptoms. This study assessed the incidence, diagnostic criteria, risk factors, and correlation with clinical response of DS based on the pooled analysis of 4 clinical trials in patients with IDH2-mutated AML treated with enasidenib as monotherapy, or in combination with azacitidine or with chemotherapy...
March 20, 2024: Blood Advances
https://read.qxmd.com/read/38507683/amyloid-fibrinogen-aggregates-microclots-predict-risks-of-disseminated-intravascular-coagulation-and-mortality
#35
JOURNAL ARTICLE
Jeremy Schofield, Simon Timothy Abrams, Rosalind Jenkins, Steven Lane, Guozheng Wang, Cheng-Hock Toh
Microclots have been associated with various conditions, including post-acute sequelae of SARS-CoV-2 infection. They have been postulated to be amyloid-fibrin(ogen) aggregates, but their role as a prognostic biomarker remains unclear. To examine for their possible clinical utility, blood samples were collected for the first 96 hours from critically ill patients (n=104) admitted to the intensive care unit (ICU). Detection was by staining platelet-poor plasma samples with Thioflavin T and visualized by fluorescent microscopy...
March 20, 2024: Blood Advances
https://read.qxmd.com/read/38507680/dissecting-causal-links-between-gut-microbiota-inflammatory-cytokines-and-dlbcl-a-mendelian-randomization-study
#36
JOURNAL ARTICLE
Peiyao Jiang, Fangfang Yu, Xiao Zhou, Huizhong Shi, Qiaomei He, Xianmin Song
Causal relationships between gut microbiota, inflammatory cytokines and diffuse large B-cell lymphoma (DLBCL) remain elusive. In addressing this gap, our Mendelian randomization (MR) study utilized data from the MiBioGen consortium encompassing 211 microbiota taxa (n= 18,340), genome-wide association study (GWAS) meta-analyses of 47 inflammatory cytokines, and DLBCL cases and controls from the FinnGen consortium (cases n = 1010, controls n = 287137). Through bidirectional MR analyses, we examined the causal links between gut microbiota and DLBCL, and employed mediation analyses, including two-step MR and multivariable MR (MVMR), to identify potential mediating inflammatory cytokines...
March 20, 2024: Blood Advances
https://read.qxmd.com/read/38502227/brentuximab-vedotin-and-chemotherapy-in-relapsed-refractory-hodgkin-lymphoma-a-propensity-score-matched-analysis
#37
JOURNAL ARTICLE
Julia Driessen, Fer de Wit, Alex F Herrera, Pier Luigi Zinzani, Ann S LaCasce, Peter D Cole, Craig H Moskowitz, Ramón García-Sanz, Michael Fuchs, Horst Mueller, Peter Borchmann, Armando Santoro, Heiko Schöder, Josée M Zijlstra, Barbara A Hutten, Alison J Moskowitz, Marie José Kersten
Several single-arm studies have explored the inclusion of brentuximab vedotin (BV) in salvage chemotherapy followed by autologous stem-cell transplantation (ASCT) for relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). However, no head-to-head comparisons with standard salvage chemotherapy have been performed. This study presents a propensity score-matched analysis encompassing individual patient data from ten clinical trials to evaluate the impact of BV in transplant-eligible R/R cHL patients. We included 768 patients, of whom 386 were treated with BV +/- chemotherapy (BV-cohort), while 382 received chemotherapy alone (chemo-cohort)...
March 19, 2024: Blood Advances
https://read.qxmd.com/read/38502198/cardiovascular-events-reported-in-patients-with-b-cell-malignancies-treated-with-zanubrutinib
#38
JOURNAL ARTICLE
Javid J Moslehi, Richard R Furman, Constantine S Tam, Joe-Elie Salem, Christopher R Flowers, Aileen Cohen, Meng Zhang, Jun Zhang, Lipeng Chen, Han Ma, Jennifer R Brown
First-generation Bruton tyrosine kinase (BTK) inhibitor ibrutinib has been associated with an increased risk for cardiovascular toxicities. Zanubrutinib is a more selective, next-generation BTK inhibitor. In this manuscript, incidence rates of atrial fibrillation, symptomatic (grade ≥2) ventricular arrhythmia, and hypertension were evaluated in a pooled analysis of 10 clinical studies with zanubrutinib monotherapy in patients (N=1550) with B-cell malignancies and a pooled analysis of head-to-head studies comparing zanubrutinib with ibrutinib (ASPEN cohort 1; ALPINE)...
March 19, 2024: Blood Advances
https://read.qxmd.com/read/38502197/cost-effectiveness-of-rapid-vs-in-house-vs-send-out-adamts13-testing-for-immune-thrombotic-thrombocytopenic-purpura
#39
JOURNAL ARTICLE
Cecily Allen, Satoko Ito, Ayesha Butt, Adriana Purcell, Rhys Richmond, Christopher A Tormey, Harlan Krumholz, Adam Cuker, George Goshua
While awaiting confirmatory results, empiric therapy for patients suspected to have immune thrombotic thrombocytopenic purpura (iTTP) provides benefits and also accrues risks and costs. Rapid assays for ADAMTS13 may be able to avoid the cost and risk exposure associated with empiric treatment. We conducted the first cost-effectiveness evaluation of testing strategies with rapid versus traditional ADAMTS13 assays in patients with intermediate to high-risk PLASMIC scores, with and without caplacizumab use. We built a Markov cohort simulation with four clinical base-case analyses: 1) Intermediate-risk PLASMIC score with caplacizumab, 2) Intermediate-risk PLASMIC score without caplacizumab, 3) High-risk PLASMIC score with caplacizumab, 4) High-risk PLASMIC score without caplacizumab...
March 19, 2024: Blood Advances
https://read.qxmd.com/read/38502195/a-phase-1-study-of-the-irreversible-flt3-inhibitor-ff-10101-in-relapsed-or-refractory-acute-myeloid-leukemia
#40
JOURNAL ARTICLE
Mark J Levis, Alexander E Perl, Gary J Schiller, Amir T Fathi, Gail J Roboz, Eunice S Wang, Jessica K Altman, Trivikram Rajkhowa, Makoto Ando, Takeaki Suzuki, Ruth Ann Subach, Gary Maier, Timothy Madden, Mary Johansen, Kin Cheung, Michael Kurman, Catherine C Smith
FLT3 tyrosine kinase inhibitors (TKIs) have clinical efficacy for patients with FLT3-mutated AML (acute myeloid leukemia), but their impact is limited by resistance in the setting of monotherapy and by tolerability problems when used in combination therapies. FF-10101 is a novel compound that covalently binds to a cysteine residue near the active site of FLT3, irreversibly inhibiting receptor signaling. It is effective against most FLT3 activating mutations, and unlike other inhibitors is minimally vulnerable to resistance induced by FLT3 ligand (FL)...
March 19, 2024: Blood Advances
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