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JOURNAL ARTICLE
Johanna Hofmann, Konstantinos Kokkaliaris
Hematopoietic stem cells (HSCs) are instrumental for organismal survival as they are responsible for lifelong production of mature blood lineages in homeostasis and response to external stress. To fulfill their function, HSCs rely on reciprocal interactions with specialized tissue microenvironments, termed HSC niches. From embryonic development to advanced aging, HSCs transition through several hematopoietic organs where they are supported by distinct extrinsic cues. Here, we describe recent discoveries on how HSC niches collectively adapt to ensure robust hematopoietic function during biological aging and following exposure to acute stress...
April 5, 2024: Blood
#22
JOURNAL ARTICLE
Tanja C Vallée, Jannik S Glasmacher, Hannes Buchner, Peter D Arkwright, Uta Behrends, Anastasia Bondarenko, Michael J Browning, David K Buchbinder, Alessandro Cattoni, Liudmyla Chernyshova, Peter Ciznar, Theresa Cole, Wojciech Czogala, Gregor Dueckers, John David M Edgar, Fatih Erbey, Anders Fasth, Francesca Ferrua, Renata Formankova, Eleonora Gambineri, Andrew R Gennery, Frederick D Goldman, Luis Ignacio Gonzalez-Granado, Carsten Heilmann, Tarja Heiskanen-Kosma, Hanna Juntti, Leena Kainulainen, Hirokazu Kanegane, Neslihan E Karaca, Sara Sebnem Kilic, Christoph Klein, Sylwia Koltan, Irina Kondratenko, Isabelle Meyts, Gulnara M Nasrullayeva, Lucia Dora Notarangelo, Srdjan Pasic, Isabelle Pellier, Claudio Pignata, Siraj Ahmed Misbah, Ansgar S Schulz, Gesmar Rs Segundo, Anna Shcherbina, Mary A Slatter, Robert Sokolic, Pere Soler-Palacin, Polina Stepensky, Joris M van Montfrans, Samppa Ryhänen, Beata Wolska-Kuśnierz, John B Ziegler, Xiaodong Zhao, Alessandro Aiuti, Hans D Ochs, Michael H Albert
WAS is a multifaceted monogenic disorder with a broad disease spectrum and variable disease severity and a variety of treatment options including allogeneic hematopoietic stem cell transplantation (HSCT) and gene therapy (GT). No reliable biomarker exists to predict disease course and outcome for individual patients. A total of 577 patients with a WAS variant from 26 countries and a median follow-up of 8.9 years (0.3-71.1), totaling 6118 patient-years, were included in this international retrospective study...
April 5, 2024: Blood
#23
JOURNAL ARTICLE
Lingjun Wang, Haoyi Wang, Mingfang Zhu, Xiaofei Ni, Lu Sun, Wanru Wang, Jie Xie, Yubin Li, Yitong Xu, Ruting Wang, Shouqing Han, Ping Zhang, Jun Peng, Ming Hou, Yu Hou
Platelet α-granules are rich in TGF-β1 which is associated with myeloid-derived suppressor cell (MDSC) biology. Responders to thrombopoietin receptor agonists (TPO-RAs) revealed a parallel increase in the number of both platelets and MDSCs. Here, anti-CD61 immune-sensitized splenocytes were transferred into severe combined immunodeficient mice to establish an active murine model of immune thrombocytopenia (ITP). Subsequently, we demonstrated that TPO-RAs augmented the inhibitory activities of MDSCs by arresting plasma cells differentiation, reducing Fas ligand expression on cytotoxic T cells, and re-balancing T cell subsets...
April 4, 2024: Blood
#24
JOURNAL ARTICLE
James Kaminski, Ryan A Fleming, Francesca Alvarez-Calderon, Marlana B Winschel, Connor McGuckin, Emily Elizabeth Ho, Fay Eng, Xianliang Rui, Paula Keskula, Lorenzo Cagnin, Joanne Charles, Jillian M Zavistaski, Steven P Margossian, Malika Kapadia, James B Rottman, Jennifer Lane, Susanne H C Baumeister, Victor Tkachev, Alex Shalek, Leslie S Kean, Ulrike Gerdemann
CAR-T cells hold promise as a therapy for B-cell-derived malignancies, yet despite their impressive initial response rates, a significant proportion of patients ultimately experience relapse. While recent studies have explored the mechanisms of in vivo CAR-T cell function, little is understood about the activation of surrounding CARneg bystander T-cells and their potential to enhance tumor responses. We performed single-cell RNA-Seq (scRNA-Seq) on non-human primate (NHP) and patient-derived T-cells to identify the phenotypic and transcriptomic hallmarks of bystander activation of CARneg T-cells following B-cell targeted CAR-T cell therapy...
April 1, 2024: Blood
#25
JOURNAL ARTICLE
Frederick L Locke, Olalekan O Oluwole, John Kuruvilla, Catherine Thieblemont, Franck Morschhauser, Gilles A Salles, Steven P Rowe, Saran Vardhanabhuti, Joshua Winters, Simone Filosto, Christina To, Paul Cheng, Marco Schupp, Ronald Korn, Marie José Kersten
Metabolic tumor volume (MTV) assessed using 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography, a measure of tumor burden, is a promising prognostic indicator in large B-cell lymphoma (LBCL). This exploratory analysis evaluated relationships between baseline MTV (categorized as low [≤median] vs high [>median]) and clinical outcomes in the phase 3 ZUMA-7 study (NCT03391466). Patients with LBCL relapsed within 12 months of or refractory to first-line chemoimmunotherapy were randomized 1:1 to axicabtagene ciloleucel (axi-cel; autologous anti-CD19 chimeric antigen receptor [CAR] T-cell therapy) or standard care (2-3 cycles of chemoimmunotherapy followed by high-dose chemotherapy with autologous stem-cell transplantation in patients who had a response)...
April 1, 2024: Blood
#26
JOURNAL ARTICLE
Annamaria Gulla, Eugenio Morelli, Megan Johnstone, Marcello Turi, Mehmet K Samur, Cirino Botta, Selma Cifric, Pietro Folino, Delaney Vinaixa, Francesca Barello, Cole Clericuzio, Vanessa Katia Favasuli, Domenico Maisano, Srikanth Talluri, Rao H Prabhala, Giada Bianchi, Mariateresa Fulciniti, Kenneth Wen, Keiji Kurata, Jiye Liu, Johany Penailillo, Alberto Bragoni, Anna Sapino, Paul G Richardson, Dharminder Chauhan, Ruben D Carrasco, Teru Hideshima, Nikhil C Munshi, Kenneth C Anderson
Immunogenic cell death (ICD) is a form of cell death by which cancer treatments can induce a clinically relevant anti-tumor immune response in a broad range of cancers. In multiple myeloma (MM), the proteasome inhibitor bortezomib is an ICD inducer and creates durable therapeutic responses in patients. However, eventual relapse and resistance to bortezomib appear inevitable. Here, by integrating patient transcriptomic data with an analysis of calreticulin (CRT) protein interactors, we found that GABARAP is a key player whose loss prevented tumor cell death from being perceived as immunogenic after bortezomib treatment...
March 29, 2024: Blood
#27
JOURNAL ARTICLE
Clémentine Sarkozy, Benoit Tessoulin, David Chiron
Mantle cell lymphoma (MCL) is a rare (5-7%), aggressive B-cell non-Hodgkin's lymphoma with well-defined hallmarks (e.g. Cyclin D1, SOX11), and whose expansion is highly dependent on the tumor microenvironment (TME). Parallel drastic progresses in the understanding of the lymphomagenesis and improved treatments led to paradigm shift in this B-cell malignancy with now prolonged disease-free survival after intensive chemotherapy and anti-CD20 based maintenance. However, this toxic strategy is not applicable in frail or elderly patients and a small but significant part of the cases will present a refractory disease representing unmet medical needs...
March 29, 2024: Blood
#28
JOURNAL ARTICLE
Yaqi Zhao, Nicholas J Short, Hagop M Kantarjian, Ti-Cheng Chang, Pankaj S Ghate, Chunxu Qu, Walid Macaron, Nitin Jain, Beenu Thakral, Aaron Phillips, Joseph D Khoury, Guillermo Garcia-Manero, Wenchao Zhang, Yiping Fan, Hui Yang, Rebecca Garris, Lewis Fady Nasr, Richard Kriwacki, Kathryn G Roberts, Marina Y Konopleva, Elias J Jabbour, Charles G Mullighan
Inotuzumab ozogamicin (InO) is an antibody-drug conjugate that delivers calicheamicin to CD22-expressing cells. In a retrospective cohort of InO-treated patients with B-cell acute lymphoblastic leukemia, we sought to understand the genomic determinants of response and resistance to InO. Pre- and post-InO patient samples were analyzed by whole genome, exome, and/or transcriptome sequencing. Acquired CD22 mutations were observed in 11% (3/27) of post-InO relapsed tumor samples, but not in refractory samples (0/16)...
March 29, 2024: Blood
#29
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
#30
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
#31
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
#32
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
#33
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
#34
JOURNAL ARTICLE
Landscape of driver mutations and their clinical effects on Down syndrome-related myeloid neoplasms.
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
#35
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
#36
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
#37
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
#38
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
#39
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
#40
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
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