journal
https://read.qxmd.com/read/38527216/excess-of-circulating-apo-transferrin-enhances-dietary-iron-absorption
#1
JOURNAL ARTICLE
Sofiya Tsyplenkova, Edouard Charlebois, Carine Fillebeen, Kostas Pantopoulos
Intravenous injection of excess apo-transferrin enhances dietary iron absorption in mice, and triggers accumulation of plasma non-transferrin bound iron (NTBI). Injected fluorescent-labeled transferrin colocalizes with lamina propria macrophages, consistent with the recently proposed iron absorption checkpoint involving macrophage-mediated transferrin degradation.
March 25, 2024: Blood
https://read.qxmd.com/read/38518106/an-oral-carbon-monoxide-releasing-molecule-protects-against-acute-hyper-hemolysis-in-sickle-cell-disease
#2
JOURNAL ARTICLE
Kim Anh Nguyen, Alessandro Matte, Roberta Foresti, Enrica Federti, Laurent Kiger, Cecile Lefebvre, Hakim Hocini, Yanis Pelinski, Hiroaki Kitagishi, Laura Bencheikh, France Pirenne, Lucia De Franceschi, Roberto Motterlini, Pablo Bartolucci
Acute hyper-hemolysis is a severe life-threatening complication in patients with sickle cell disease (SCD) that may occur during delayed hemolytic transfusion reaction (DHTR), or vaso-occlusive crises associated with multi-organ failure. Here, we developed in vitro and in vivo animal models to mimic endothelial damage during the early phase of hyper-hemolysis in SCD. We then used the carbon monoxide (CO)-releasing molecule CORM-401 and examined its effects against endothelial activation, damage, and inflammation inflicted by hemolysates containing red blood cell membrane-derived particles...
March 22, 2024: Blood
https://read.qxmd.com/read/38518105/the-il-7r-antagonist-lusvertikimab-reduces-leukemic-burden-in-xenograft-all-via-antibody-dependent-cellular-phagocytosis
#3
JOURNAL ARTICLE
Lennart Lenk, Irène Baccelli, Anna Laqua, Julia Heymann, Claas Reimer, Anna Dietterle, Dorothee Winterberg, Caroline Mary, Frédérique Corallo, Julien Taurelle, Emma Narbeburu, Stéphanie Lara Neyton, Mylène Déramé, Sabrina Pengam, Fotini Vogiatzi, Beat Bornhauser, Jean-Pierre Bourquin, Simon Raffel, Vladyslava Dovhan, Thomas Schüler, Gabriele Escherich, Monique L den Boer, Judith M Boer, Wiebke Wessels, Matthias Peipp, Julia Alten, Željko Antić, Anke Katharina Bergmann, Martin Schrappe, Gunnar Cario, Monika Brüggemann, Nicolas Poirier, Denis M Schewe
Acute lymphoblastic leukemia (ALL) arises from the uncontrolled proliferation of precursor B or T cells (BCP- or T-ALL). Current treatment protocols obtain high cure rates in children but are based on toxic polychemotherapy. Novel therapies are urgently needed, especially in relapsed/refractory (r/r) disease, high-risk leukemias and T-ALL, where immunotherapy approaches remain scarce. While the Interleukin-7 receptor (IL-7R) plays a pivotal role in ALL development, no IL-7R-targeting immunotherapy has yet reached clinical application in ALL...
March 22, 2024: Blood
https://read.qxmd.com/read/38518104/genomic-imbalances-analysis-provides-new-insight-into-prognostic-factors-in-adult-and-pediatric-t-all
#4
JOURNAL ARTICLE
Estelle Balducci, Mathieu Simonin, Nicolas Duployez, Thomas Steimlé, Marie-Emilie Dourthe, Patrick Villarese, Stéphane Ducassou, Isabelle Arnoux, Jean-Michel Cayuela, Marie Balsat, Lucien Courtois, Guillaume P Andrieu, Aurore Touzart, Françoise Huguet, Arnaud Petit, Norbert Ifrah, Herve Dombret, André Baruchel, Elizabeth A Macintyre, Claude Preudhomme, Nicolas Boissel, Vahid Asnafi
Given the poor outcome of refractory and relapsing T-ALL, identifying prognostic markers is still challenging. Using SNP-array analysis, we provide a comprehensive analysis of genomic imbalances in a cohort of 317 newly-diagnosed T-ALL patients including 135 children and 182 adults with respect to clinical and biological features and outcomes. SNP-array results identified at least one somatic genomic imbalance in virtually all T-ALL patients (~96%). Del(9)(p21) (~70%) and UPD(9)p21)/CDKN2A/B (~28%) were the most frequent genomic imbalances...
March 22, 2024: Blood
https://read.qxmd.com/read/38518102/endothelial-zip8-plays-a-minor-role-in-bmp6-regulation-by-iron-in-mice
#5
JOURNAL ARTICLE
Allison L Fisher, Sydney Phillips, Chia-Yu Wang, Joao A Paulo, Xia Xiao, Gillian A Moschetta, Adhvaith Sridhar, Joseph D Mancias, Jodie L Babitt
Iron-mediated induction of BMP6 expression by liver endothelial cells is essential for iron homeostasis regulation. We utilized multiple dietary and genetic mouse cohorts to demonstrate a minor functional role for ZIP8 in regulating BMP6 expression under high-iron conditions.
March 22, 2024: Blood
https://read.qxmd.com/read/38513239/landscape-of-driver-mutations-and-their-clinical-effects-on-down-syndrome-related-myeloid-neoplasms
#6
JOURNAL ARTICLE
Tomohiko Sato, Kenichi Yoshida, Tsutomu Toki, Rika Kanezaki, Kiminori Terui, Ryunosuke Saiki, Masami Ojima, Yotaro Ochi, Seiya Mizuno, Masaharu Yoshihara, Tamayo Uechi, Naoya Kenmochi, Shiro Tanaka, Jun Matsubayashi, Kenta Kisai, Ko Kudo, Kentaro Yuzawa, Yuka Takahashi, Tatsuhiko Tanaka, Yohei Yamamoto, Akie Kobayashi, Takuya Kamio, Shinya Sasaki, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Hideki Muramatsu, Asahito Hama, Daisuke Hasegawa, Atsushi Sato, Katsuyoshi Koh, Shuhei Karakawa, Masao Kobayashi, Junichi Hara, Yuichi Taneyama, Chihaya Imai, Daiichiro Hasegawa, Naoto Fujita, Masahiro Yoshitomi, Shotaro Iwamoto, Genki Yamato, Satoshi Saida, Nobutaka Kiyokawa, Takao Deguchi, Masafumi Ito, Hidemasa Matsuo, Souichi Adachi, Yasuhide Hayashi, Takashi Taga, Akiko Moriya Saito, Keizo Horibe, Kenichiro Watanabe, Daisuke Tomizawa, Satoru Miyano, Satoru Takahashi, Seishi Ogawa, Etsuro Ito
Transient abnormal myelopoiesis (TAM) is a common complication in newborns with Down syndrome (DS). It commonly progresses to myeloid leukemia (ML-DS) after spontaneous regression. In contrast to the favorable prognosis of primary ML-DS, patients with refractory/relapsed ML-DS have poor outcomes. However, the molecular basis for refractoriness and relapse, and the full spectrum of driver mutations in ML-DS remain largely unknown. We conducted a genomic profiling study of 143 TAM, 204 ML-DS, and 34 non-DS acute megakaryoblastic leukemia cases, including 39 ML-DS cases analyzed by exome sequencing...
March 21, 2024: Blood
https://read.qxmd.com/read/38513237/genetic-regulation-of-carnitine-metabolism-controls-lipid-damage-repair-and-aging-rbc-hemolysis-in-vivo-and-in-vitro
#7
JOURNAL ARTICLE
Travis Nemkov, Alicia Key, Daniel Stephenson, Eric J Earley, Gregory R Keele, Ariel M Hay, Pascal Amireault, Madeleine Casimir, Michaël Dussiot, Monika Dzieciatkowska, Julie A Reisz, Xutao Deng, Mars Stone, Steven H Kleinman, Steven L Spitalnik, Kirk C Hansen, Philip J Norris, Gary A Churchill, Michael P Busch, Nareg H Roubinian, Grier P Page, James C Zimring, Arduino Arduini, Angelo D'Alessandro
Recent large-scale multi-omics studies suggest that genetic factors influence the chemical individuality of donated blood. To examine this concept, we performed metabolomics analyses of 643 blood units from volunteers who donated units of packed red blood cells (RBCs) on two separate occasions. These analyses identified carnitine metabolism as the most reproducible pathway across multiple donations from the same donor. We also measured L-carnitine and acyl-carnitines in 13,091 packed RBC units from donors in the Recipient Epidemiology and Donor Evaluation (REDS) study...
March 21, 2024: Blood
https://read.qxmd.com/read/38513233/paroxysmal-nocturnal-hemoglobinuria-related-thrombosis-in-the-era-of-novel-therapies-a-2043-patient-years-analysis
#8
JOURNAL ARTICLE
Carmelo Gurnari, Hussein Awada, Simona Pagliuca, Danai Dima, Fauzia Ullah, Naomi Kawashima, Yasuo Kubota, Ceylan Colak, Valeria Visconte, Bhumika J Patel, Vikram Dhillon, Naimisha Marneni, Suresh Kumar Balasubramanian, Ashwin Kishtagari, Taha Bat, Jaroslaw P Maciejewski
Thrombophilia is one of the principal features of paroxysmal nocturnal hemoglobinuria (PNH) and constitutes the main cause of disease morbidity/mortality. Anti-complement treatment has revolutionized the natural history of PNH with control of the hemolytic process and abolition of thrombotic events (TE). However, no guidelines exist for the management of thromboembolic complications in this setting, with type and duration of anti-coagulation depending on individual practices. Besides, a scarcity of data is present on the efficacy of direct oral anti-coagulants (DOACs)...
March 21, 2024: Blood
https://read.qxmd.com/read/38502824/peak-adamts13-activity-to-assess-adamts13-conformation-and-risk-of-relapse-in-immune-mediated-thrombotic-thrombocytopenic-purpura
#9
JOURNAL ARTICLE
Nithya Prasannan, Bertina Dragunaite, Maryam Owais Subhan, Mari Thomas, Rens de Groot, Deepak Singh, Karen Vanhoorelbeke, Marie Scully
Previous studies have demonstrated that more than 38% of immune-mediated thrombotic thrombocytopenic purpura (TTP) patients in remission with activity >50% had an open ADAMTS13 conformation. We assessed ADAMTS13 conformation in remission (ADAMTS13 activity >60%), focussing on peak ADAMTS13 activity levels and longitudinal assessment in 420 samples across 157 patients. Fewer cases had open conformation at peak ADAMTS13 activity compared to unselected remission samples with ADAMTS13 activity>60% (23% vs 43%)...
March 19, 2024: Blood
https://read.qxmd.com/read/38498174/frontline-treatment-of-mantle-cell-lymphoma
#10
JOURNAL ARTICLE
Christine E Ryan, Philippe Armand, Ann S LaCasce
Despite many recent therapeutic advances, mantle cell lymphoma (MCL) remains a largely incurable disease. Treatments for patients with relapsed/refractory (R/R) disease are limited in number and in response durability. Therefore, improving the efficacy of frontline (1L) treatment, and specifically maximizing the duration of first remission, remains of critical importance to obtain favorable long-term outcomes. As 1L treatments become more effective, improving tolerability is also becoming an increasingly realistic goal...
March 18, 2024: Blood
https://read.qxmd.com/read/38498044/evidence-for-antigen-presentation-by-human-neutrophils
#11
JOURNAL ARTICLE
Angus Moffat, Emily Gwyer Findlay
Neutrophils are the first migrating responders to sterile and infectious inflammation, and act in a powerful but non-specific fashion to kill a wide variety of pathogens. It is now clear that they can also act in a highly discriminating fashion; this is particularly evident in their interactions with other cells of the immune system. It is clear that neutrophils are present during the adaptive immune response, interacting with T cells in complex ways which differ between tissue types and disease state. One of the ways in which this interaction is mediated is by neutrophil expression of HLA molecules and presentation of antigen to T cells...
March 18, 2024: Blood
https://read.qxmd.com/read/38498041/thrombosis-risk-in-double-heterozygous-carriers-of-factor-v-leiden-and-prothrombin-g20210a-in-finngen-and-the-uk-biobank
#12
JOURNAL ARTICLE
Justine Ryu, Joel T Rämö, Sean Joseph Jurgens, Teemu Niiranen, Simone Sanna-Cherchi, Kenneth A Bauer, Amelia Haj, Seung Hoan Choi, Aarno Palotie, Mark Daly, Patrick T Ellinor, Pavan K Bendapudi
The Factor V Leiden (FVL, rs6025) and prothrombin G20210A (PTGM, rs1799963) polymorphisms are two of the most well-studied genetic risk factors for venous thromboembolism (VTE). However, double heterozygosity (DH) for FVL and PTGM remains poorly understood, with prior studies in marked disagreement about the thrombosis risk conferred by the DH genotype. Utilizing multi-dimensional data from the UK Biobank (UKB) and the FinnGen biorepositories, we evaluated the clinical impact of DH carrier status across 937,939 individuals...
March 18, 2024: Blood
https://read.qxmd.com/read/38498036/a-lineage-specific-stat5bn642h-mouse-model-to-study-nk-cell-leukemia
#13
JOURNAL ARTICLE
Klara Klein, Sebastian Kollmann, Angela Hiesinger, Julia List, Jonatan Kendler, Thorsten Klampfl, Mehak Randhawa, Jana Trifinopoulos, Barbara Maurer, Reinhard Grausenburger, Christof A Bertram, Richard H Moriggl, Thomas Rülicke, Charles G Mullighan, Agnieszka Witalisz-Siepracka, Wencke Walter, Gregor Hoermann, Veronika Sexl, Dagmar Gotthardt
Patients with T- and NK-cell neoplasms frequently have somatic STAT5B gain-of-function mutations. The most frequent STAT5B mutation is STAT5BN642H, which is known to drive murine T-cell leukemia although its role in NK-cell malignancies is unclear. Introduction of the STAT5BN642H mutation into human NK-cell lines enhances their potential to induce leukemia in mice. We have generated a mouse model that enables tissue-specific expression of STAT5BN642H and have selectively expressed the mutated STAT5B in hematopoietic cells (N642Hvav/+) or exclusively in NK cells (N642HNK/NK)...
March 18, 2024: Blood
https://read.qxmd.com/read/38498034/malignant-progression-of-pre-leukemic-disorders
#14
JOURNAL ARTICLE
Trent Hall, Sandeep Gurbuxani, John D Crispino
The spectrum of myeloid disorders ranges from aplastic bone marrow failure characterized by an empty bone marrow completely lacking in hematopoiesis to acute myeloid leukemia where the marrow space is replaced by undifferentiated leukemic blasts. Recent advances in the capacity to sequence bulk tumor population as well as at a single cell level has provided significant insight into the stepwise process of transformation to acute myeloid leukemia. Using models of progression in the context of germline predisposition (trisomy 21, GATA2 deficiency, SAMD9/9L syndrome), premalignant states (clonal hematopoiesis and clonal cytopenia of unknown significance) and myelodysplastic syndrome, we review the mechanisms of progression focusing on the hierarchy of clonal mutation and potential roles of transcription factor alterations, splicing factor mutations and the bone marrow environment in progression to acute myeloid leukemia...
March 18, 2024: Blood
https://read.qxmd.com/read/38498025/the-tlk-asf1-histone-chaperone-pathway-plays-a-critical-role-in-il-1b-mediated-aml-progression
#15
JOURNAL ARTICLE
Hsin-Yun Lin, Mona M Hosseini, John McClatchy, Marina Villamor-Payà, Sophia Jeng, Daniel Bottomly, Chia-Feng Tsai, Camilo Posso, Jeremy Jacobson, Andrew C Adey, Sara J C Gosline, Tao Liu, Shannon K McWeeney, Travis H Stracker, Anupriya Agarwal
Identifying and targeting microenvironment-driven pathways that are active across acute myeloid leukemia (AML) genetic subtypes should allow the development of more broadly effective therapies. The pro-inflammatory cytokine IL-1 is abundant in the AML microenvironment and promotes leukemic growth. Through RNA-sequencing analysis, we identify that IL-1 upregulated ASF1B (anti-silencing function-1B), a histone chaperone, in AML progenitors compared to healthy progenitors. ASF1B, along with its paralogous protein ASF1A recruits H3-H4 histones onto the replication fork during S-phase, a process regulated by tousled-like kinase 1 and 2 (TLKs)...
March 18, 2024: Blood
https://read.qxmd.com/read/38493486/2023-annual-meeting-abstract-178791-retraction
#16
JOURNAL ARTICLE
Cy R Wilkins
No abstract text is available yet for this article.
March 17, 2024: Blood
https://read.qxmd.com/read/38493484/management-of-adult-patients-with-cmml-undergoing-allo-hct-recommendations-from-the-ebmt-ph-g-committee
#17
JOURNAL ARTICLE
Francesco Onida, Nico Gagelmann, Yves Chalandon, Guido Kobbe, Marie Robin, Argiris Symeonidis, Theo M de Witte, Raphaël A Itzykson, Madlen Jentzsch, Uwe Platzbecker, Valeria Santini, Guillermo F Sanz, Christoph Scheid, Eric Solary, Peter Valent, Raffaela Greco, Isabel Sánchez-Ortega, Ibrahim Yakoub-Agha, Lisa Pleyer
Chronic myelomonocytic leukemia (CMML) is a heterogeneous disease presenting with either myeloproliferative or myelodysplastic features. Allogeneic hematopoietic cell transplantation (allo-HCT) remains the only potentially curative option, but the inherent toxicity of this procedure makes the decision to proceed to allo-HCT challenging, particularly as patients with CMML are mostly older and comorbid. Therefore, the decision between a non-intensive treatment approach and allo-HCT represents a delicate balance, especially since prospective randomized studies are lacking and retrospective data in the literature is conflicting...
March 17, 2024: Blood
https://read.qxmd.com/read/38493482/an-international-learning-collaborative-phase-2-trial-for-haploidentical-bone-marrow-transplant-in-sickle-cell-disease
#18
JOURNAL ARTICLE
Adetola A Kassim, Josu de la Fuente, Erfan Nur, Karina Wilkerson, Ali Alahmari, Adriana Seber, Carmem M S Bonfim, Belinda Pinto Simões, Mohsen Alzahrani, Michael J Eckrich, Biljana Horn, Rabi Hanna, Nathalie Dhedin, Hemalatha G Rangarajan, Roseane Vasconcelos Gouveia, Fahad Almohareb, Mahmoud Aljurf, Mohammed Essa, Bader Alahmari, Katie S Gatwood, James A Connelly, Elisabeth Dovern, Mark Rodeghier, Michael R DeBaun
In the setting of a learning collaborative, we conducted an international multicenter phase 2 clinical trial testing the hypothesis that non-myeloablative related haploidentical BMT with thiotepa and post-transplant cyclophosphamide (PTCy) will result in 2-year event-free survival (no graft failure or death) of at least 80%. A total of 70 participants (median age 19.1 (IQR 14.1 - 25.0) were evaluable based on the conditioning protocol. Graft failure occurred in 11.4% (8/70) and only in participants <18 years (p=0...
March 17, 2024: Blood
https://read.qxmd.com/read/38493481/loss-of-dnmt3a-increased-self-renewal-and-resistance-to-pegifn%C3%AE-in-jak2-v617f-positive-myeloproliferative-neoplasms
#19
JOURNAL ARTICLE
Marc Usart, Jan Stetka, Damien Luque Paz, Nils Hansen, Quentin Kimmerlin, Tiago Almeida Fonseca, Melissa Lock, Lucia Kubovcakova, Riikka Karjalainen, Hui Hao-Shen, Anastasiya Börsch, Athimed El Taher, Jessica Schulz, Jean-Christophe Leroux, Stefan Dirnhofer, Radek C Skoda
Pegylated interferon alpha (pegIFNα) can induce molecular remissions in JAK2-V617F-positive myeloproliferative neoplasms (MPN) patients by targeting long-term hematopoietic stem cells (LT-HSCs). Additional somatic mutations in genes regulating LT-HSC self-renewal, such as DNMT3A, have been reported to have poorer responses to pegIFNα. We investigated if DNMT3A loss leads to alterations in JAK2-V617F LT-HSCs functions conferring resistance to pegIFNα treatment in a mouse model of MPN and in hematopoietic progenitors from MPN patients...
March 17, 2024: Blood
https://read.qxmd.com/read/38493479/integration-of-%C3%AE-deficient-cars-into-the-cd3-zeta-gene-conveys-potent-cytotoxicity-in-t-and-nk-cells
#20
JOURNAL ARTICLE
Jonas Kath, Clemens Franke, Vanessa Drosdek, Weijie Du, Viktor Glaser, Carla Fuster-Garcia, Maik Stein, Tatiana Zittel, Sarah Schulenberg, Caroline E Porter, Lena Andersch, Annette Künkele, Joshua Alcaniz, Jens Hoffmann, Hinrich Abken, Mohamed Abou-El-Enein, Axel Pruß, Masataka Suzuki, Toni Cathomen, Renata Stripecke, Hans-Dieter Volk, Petra Reinke, Michael Schmueck-Henneresse, Dimitrios Laurin Wagner
Chimeric antigen receptor (CAR)-redirected immune cells hold significant therapeutic potential for oncology, autoimmune diseases, transplant medicine, and infections. All approved CAR-T therapies rely on personalized manufacturing using undirected viral gene transfer, which results in non-physiological regulation of CAR-signaling and limits their accessibility due to logistical challenges, high costs and biosafety requirements. Random gene transfer modalities pose a risk of malignant transformation by insertional mutagenesis...
March 17, 2024: Blood
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