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Takeda K, Cretney E, Hayakawa Y, Ota T, Akiba H, Ogasawara K, Yagita H, Kinoshita K, Okumura K, Smyth MJ. TRAIL identifies immature natural killer cells in newborn mice and adult mouse liver. Blood. 2005;105(5):2082-2089. Blood (IF 20.3) Pub Date : 2023-11-23 Cme Account
The Editors of Blood retract the 1 March 2005 paper cited above. Concerns regarding the duplication of several outlying data points in Figure 4 were brought to the journal's attention. A search for original source data was unsuccessful. As a result, the data underlying this figure cannot be validated, and the paper has been retracted. Yoshihiro Hayakawa, Kouetsu Ogasawara, Ko Okumura, Kazuyoshi Takeda
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A human genome editing-based MLL::AF4 ALL model recapitulates key cellular and molecular leukemogenic features. Blood (IF 20.3) Pub Date : 2023-11-16 Clara Bueno,Raul Torres-Ruiz,Talia Velasco-Hernandez,Oscar Molina,Paolo Petazzi,Alba Martinez,Virginia Rodriguez,Meritxell Vinyoles,Sandra Cantilena,Owen Williams,Nerea Vega-Garcia,Sandra Rodriguez-Perales,Jose C Segovia,Oscar Quintana-Bustamante,Anindita Roy,Claus Meyer,Rolf Marschalek,Alastair L Smith,Thomas A Milne,Mario F Fraga,Juan Ramón Tejedor,Pablo Menéndez
Cellular ontogeny and MLL breakpoint site influence the capacity of MLL-edited CD34+ hematopoietic cells to initiate and recapitulate infant patients' features in pro-B-cell acute lymphoblastic leukemia (B-ALL). We provide key insights into the leukemogenic determinants of MLL-AF4+ infant B-ALL.
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Loss of function of ENT3 drives histiocytosis and inflammation through TLR-MAPK signaling. Blood (IF 20.3) Pub Date : 2023-11-16 Ruth Shiloh,Ruth Lubin,Odeya David,Ifat Geron,Elimelech Okon,Idit Hazan,Marketa Zaliova,Gil Amarilyo,Yehudit Birger,Yael Borovitz,Dafna Brik,Arnon Broides,Sarit Cohen-Kedar,Liora Harel,Eyal Kristal,Daria Kozlova,Galina Ling,Mika Shapira Rootman,Noa Shefer Averbuch,Shiri Spielman,Jan Trka,Shai Izraeli,Simon Yona,Sarah Elitzur
Histiocytoses are inflammatory myeloid neoplasms often driven by somatic activating mutations in mitogen-activated protein kinase (MAPK) cascade genes. H syndrome is an inflammatory genetic disorder caused by germ line loss-of-function mutations in SLC29A3, encoding the lysosomal equilibrative nucleoside transporter 3 (ENT3). Patients with H syndrome are predisposed to develop histiocytosis, yet the
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Neutral sphingomyelinase blockade enhances hematopoietic stem cell fitness through an integrated stress response. Blood (IF 20.3) Pub Date : 2023-11-16 Stephanie N Hurwitz,Seul K Jung,Danielle R Kobulsky,Hossein Fazelinia,Lynn A Spruce,Empar Baltasar Pérez,Nathalie Groen,Clementina Mesaros,Peter Kurre
Hematopoietic stem and progenitor cell (HSPC) transplantation serves as a curative therapy for many benign and malignant hematopoietic disorders and as a platform for gene therapy. However, growing needs for ex vivo manipulation of HSPC-graft products are limited by barriers in maintaining critical self-renewal and quiescence properties. The role of sphingolipid metabolism in safeguarding these essential
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How I treat transplant-eligible patients with myelofibrosis. Blood (IF 20.3) Pub Date : 2023-11-16 Nicolaus Kröger,Christine Wolschke,Nico Gagelmann
Despite the approval of Janus kinase inhibitors and novel agents for patients with myelofibrosis (MF), disease-modifying responses remain limited, and hematopoietic stem cell transplantation (HSCT) remains the only potentially curative treatment option. The number of HSCTs for MF continues to increase worldwide, but its inherent therapy-related morbidity and mortality limit its use for many patients
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Fractionated vs single-dose gemtuzumab ozogamicin with determinants of benefit in older patients with AML: the UK NCRI AML18 trial. Blood (IF 20.3) Pub Date : 2023-11-16 Sylvie D Freeman,Abin Thomas,Ian Thomas,Robert K Hills,Paresh Vyas,Amanda Gilkes,Marlen Metzner,Niels Asger Jakobsen,Alison Kennedy,Rachel Moore,Nuria Marquez Almuina,Sarah Burns,Sophie King,Georgia Andrew,Kathleen M E Gallagher,Rob S Sellar,Paul Cahalin,Duruta Weber,Mike Dennis,Priyanka Mehta,Steven Knapper,Nigel H Russell
Addition of gemtuzumab ozogamicin (GO) to induction chemotherapy improves outcomes in older patients with acute myeloid leukemia (AML), but it is uncertain whether a fractionated schedule provides additional benefit to a single dose. We randomized 852 older adults (median age, 68-years) with AML/high-risk myelodysplasia to GO on day 1 (GO1) or on days 1 and 4 (GO2) of course 1 induction. The median
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Hereditary transthyretin amyloidosis in the era of RNA interference, antisense oligonucleotide, and CRISPR-Cas9 treatments. Blood (IF 20.3) Pub Date : 2023-11-09 David Adams,Vincent Algalarrondo,Andoni Echaniz-Laguna
Hereditary transthyretin amyloidosis (ATTRv) is a rare autosomal dominant adult-onset disorder caused by point mutations in the transthyretin (TTR) gene encoding TTR, also known as prealbumin. ATTRv survival ranges from 3 to 10 years, and peripheral nervous system and heart are usually the 2 main tissues affected, although central nervous system and eye may also be involved. Because the liver is the
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The iron chaperone poly(rC)-binding protein 1 regulates iron efflux through intestinal ferroportin in mice. Blood (IF 20.3) Pub Date : 2023-11-09 Yubo Wang,Olga Protchenko,Kari D Huber,Minoo Shakoury-Elizeh,Manik C Ghosh,Caroline C Philpott
Iron is an essential nutrient required by all cells but used primarily for red blood cell production. Because humans have no effective mechanism for ridding the body of excess iron, the absorption of dietary iron must be precisely regulated. The critical site of regulation is the transfer of iron from the absorptive enterocyte to the portal circulation via the sole iron efflux transporter, ferroportin
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Loss of endothelial membrane KIT ligand affects systemic KIT ligand levels but not bone marrow hematopoietic stem cells. Blood (IF 20.3) Pub Date : 2023-11-09 Sahoko Matsuoka,Raffaella Facchini,Tiago C Luis,Joana Carrelha,Petter S Woll,Takuo Mizukami,Bishan Wu,Hanane Boukarabila,Mario Buono,Ruggiero Norfo,Fumio Arai,Toshio Suda,Adam J Mead,Claus Nerlov,Sten Eirik W Jacobsen
A critical regulatory role of hematopoietic stem cell (HSC) vascular niches in the bone marrow has been implicated to occur through endothelial niche cell expression of KIT ligand. However, endothelial-derived KIT ligand is expressed in both a soluble and membrane-bound form and not unique to bone marrow niches, and it is also systemically distributed through the circulatory system. Here, we confirm
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Innovations in RNA therapy for hemophilia. Blood (IF 20.3) Pub Date : 2023-11-09 Margaret V Ragni,Stephen Y Chan
Given the shortcomings of current factor-, nonfactor-, and adeno-associated virus gene-based therapies, the recent advent of RNA-based therapeutics for hemophilia is changing the fundamental approach to hemophilia management. From small interfering RNA therapeutics that knockdown clot regulators antithrombin, protein S, and heparin cofactor II, to CRISPR/Cas9 gene editing that may personalize treatment
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The oxylipin analog CS585 prevents platelet activation and thrombosis through activation of the prostacyclin receptor. Blood (IF 20.3) Pub Date : 2023-11-02 Livia Stanger,Adriana Yamaguchi,Pooja Yalavarthi,Sylviane Lambert,Devin Gilmore,Andrew Rickenberg,Catherine Luke,Kiran Kumar,Andrea T Obi,Andrew White,Niklas Bergh,Björn Dahlöf,Michael Holinstat
Cardiovascular disease remains the primary cause of morbidity and mortality globally. Platelet activation is critical for maintaining hemostasis and preventing the leakage of blood cells from the vessel. There has been a paucity in the development of new drugs to target platelet reactivity. Recently, the oxylipin 12(S)-hydroxy-eicosatrienoic acid (12-HETrE), which is produced in platelets, was shown
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BRAF V600E is associated with higher incidence of second cancers in adults with Langerhans cell histiocytosis. Blood (IF 20.3) Pub Date : 2023-11-02 Aldo A Acosta-Medina,Paul G Kemps,Timo C E Zondag,Jithma P Abeykoon,Jelske Forma-Borst,Eline C Steenwijk,Elizabeth A M Feijen,Jop C Teepen,N Nora Bennani,Susan M Schram,Mithun V Shah,Caroline Davidge-Pitts,Matthew J Koster,Jay H Ryu,Robert Vassallo,W Oliver Tobin,Jason R Young,Surendra Dasari,Karen Rech,Aishwarya Ravindran,Arjen H G Cleven,Robert M Verdijk,Carel J M van Noesel,Brian V Balgobind,Gerrit
In this retrospective study, BRAF mutation status did not correlate with disease extent or (event-free) survival in 156 adults with Langerhans cell histiocytosis. BRAFV600E was associated with an increased incidence of second malignancies, often comprising hematological cancers, which may be clonally related.
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LepR+ niche cell-derived AREG compromises hematopoietic stem cell maintenance under conditions of DNA repair deficiency and aging. Blood (IF 20.3) Pub Date : 2023-11-02 Limei Wu,Qiqi Lin,Srinivas Chatla,Surya Amarachintha,Andrew F Wilson,Neha Atale,Zhenxia J Gao,Jonathan Joseph,Emily V Wolff,Wei Du
The cross talk between extrinsic niche-derived and intrinsic hematopoietic stem cell (HSC) factors controlling HSC maintenance remains elusive. Here, we demonstrated that amphiregulin (AREG) from bone marrow (BM) leptin receptor (LepR+) niche cells is an important factor that mediates the cross talk between the BM niche and HSCs in stem cell maintenance. Mice deficient of the DNA repair gene Brca2
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CARD11 gain of function upregulates BCL2A1 expression and promotes resistance to targeted therapies combination in B-cell lymphoma. Blood (IF 20.3) Pub Date : 2023-11-02 Salomé Decombis,Celine Bellanger,Yannick Le Bris,Candice Madiot,Jane Jardine,Juliana Carvalho Santos,Delphine Boulet,Christelle Dousset,Audrey Menard,Charlotte Kervoelen,Elise Douillard,Philippe Moreau,Stephane Minvielle,Agnes Moreau-Aubry,Benoit Tessoulin,Gael Roue,Nicolas Bidère,Steven Le Gouill,Catherine Pellat-Deceunynck,David Chiron
A strategy combining targeted therapies is effective in B-cell lymphomas (BCL), such as mantle cell lymphoma (MCL), but acquired resistances remain a recurrent issue. In this study, we performed integrative longitudinal genomic and single-cell RNA-sequencing analyses of patients with MCL who were treated with targeted therapies against CD20, BCL2, and Bruton tyrosine kinase (OAsIs trial). We revealed
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Lenalidomide and dexamethasone maintenance with or without ixazomib, tailored by residual disease status in myeloma. Blood (IF 20.3) Pub Date : 2023-11-02 Laura Rosiñol,Albert Oriol,Rafael Ríos,María Jesús Blanchard,Isidro Jarque,Joan Bargay,Miguel Teodoro Hernández,Valentín Cabañas,Estrella Carrillo-Cruz,Anna Sureda,Joaquín Martínez-López,Isabel Krsnik,Maria Esther González,Luis Felipe Casado,Josep María Martí,Cristina Encinas,Felipe de Arriba,Luis Palomera,Antonia Sampol,Yolanda González-Montes,Elena Cabezudo,Bruno Paiva,Noemí Puig,María Teresa Cedena
From November 2014 to May 2017, 332 patients homogeneously treated with bortezomib, lenalidomide, and dexamethasone (VRD) induction, autologous stem cell transplant, and VRD consolidation were randomly assigned to receive maintenance therapy with lenalidomide and dexamethasone (RD; 161 patients) vs RD plus ixazomib (IRD; 171 patients). RD consisted of lenalidomide 15 mg/d from days 1 to 21 plus dexamethasone
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Potential future direction of measurable residual disease evaluation in multiple myeloma. Blood (IF 20.3) Pub Date : 2023-11-02 Mohamad Mohty,Hervé Avet-Loiseau,Florent Malard,Jean-Luc Harousseau
Multiple myeloma remains an incurable disease plagued by high relapse rates. Deeper and more sustainable responses, however, have been consistently shown to improve outcomes and could eventually pave the way to achieving a cure. Our understanding of disease response has surpassed complete response (CR), because the current definitions are suboptimal, and the treatment goal should aim even beyond stringent
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Two-year follow-up of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma in TRANSCEND NHL 001. Blood (IF 20.3) Pub Date : 2023-10-27 Jeremy S Abramson,M Lia Palomba,Leo I Gordon,Matthew A Lunning,Michael L Wang,Jon E Arnason,Enkhtsetseg Purev,David G Maloney,Charalambos Babis Andreadis,Alison Sehgal,Scott R Solomon,Nilanjan Ghosh,Christine Dehner,Yeonhee Kim,Ken Ogasawara,Ana Kostic,Tanya Siddiqi
Lisocabtagene maraleucel (liso-cel) demonstrated significant efficacy with a manageable safety profile as third-line or later treatment in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) in the TRANSCEND NHL 001 study. Primary end points were adverse events (AE), dose-limiting toxicities, and objective response rate (ORR) per independent review committee. Key secondary end points
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Differentiation of BCMA-specific induced pluripotent stem cells into CD8αβ+ T cells targeting multiple myeloma. Blood (IF 20.3) Pub Date : 2023-10-27 Jooeun Bae,Shuichi Kitayama,Zach Herbert,Laurence Daheron,Keiji Kurata,Derin Keskin,Kenneth Livak,Shuqiang Li,Mubin Tarannum,Rizwan Romee,Mehmet K Samur,Nikhil C Munshi,Shin Kaneko,Jerome Ritz,Kenneth C Anderson
A major hurdle in adoptive T cell therapy is cell exhaustion and failure to maintain anti-tumor responses. Here, we introduce an induced pluripotent stem cell (iPSC) strategy for reprogramming and revitalization of precursor exhausted BCMA-specific T cells to effectively target multiple myeloma (MM). Heteroclitic BCMA72-80 (YLMFLLRKI)-specific CD8+ memory cytotoxic T lymphocytes (CTL) were epigenetically
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Acute myeloid leukemias with UBTF tandem duplications are sensitive to Menin inhibitors. Blood (IF 20.3) Pub Date : 2023-10-27 Juan Martin Barajas,Milad Rasouli,Masayuki Umeda,Ryan Lea Hiltenbrand,Sherif Abdelhamed,Rebecca Mohnani,Bright Arthur,Tamara Westover,Melvin E Thomas,Minoo Ashtiani,Laura J Janke,Beisi Xu,Ti-Cheng Chang,Wojciech Rosikiewicz,Emily Xiong,Chandra Rolle,Jonathan Low,Reethu Krishnan,Guangchun Song,Michael P Walsh,Jing J Ma,Jeffrey E Rubnitz,Ilaria Iacobucci,Taosheng Chen,Anja Krippner-Heidenreich,Christian
UBTF tandem duplications (UBTF-TDs) have recently emerged as a recurrent alteration in pediatric and adult acute myeloid leukemia (AML). UBTF-TD leukemias are characterized by a poor response to conventional chemotherapy and a transcriptional signature that mirrors NUP98-rearranged and NPM1-mutant AMLs, including HOX gene dysregulation. However, the mechanism of how UBTF-TD drives leukemogenesis remains
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Rethinking Coagulation: From enzymatic and cell-based reactions to a convergent model involving innate immune activation. Blood (IF 20.3) Pub Date : 2023-10-27 Jun Yong,Cheng-Hock Toh
Advancements in the conceptual thinking of haemostasis and thrombosis have been catalysed by major developments within health research over several decades. The cascade model of coagulation was first described in the 1960s when biochemistry gained prominence through innovative experimentation and technical developments. This was followed by the cell-based model which integrated cellular coordination
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Hemocompatibility and Biophysical Interface of Left Ventricular Assist Devices and Total Artificial Hearts. Blood (IF 20.3) Pub Date : 2023-10-27 Angelo Nascimbene,David Bark,David M Smadja
Over the past two decades, there has been a significant increase in the utilization of long-term mechanical circulatory support (MCS) for the treatment of cardiac failure. Left ventricular assist devices (LVADs) and total artificial hearts (TAHs) have been developed in parallel to serve as bridge-to-transplant and destination therapy solutions. Despite the distinct hemodynamic characteristics introduced
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The Challenge of Clinical Endpoints in Sickle Cell Disease. Blood (IF 20.3) Pub Date : 2023-10-27 Kenneth I Ataga
As most patients with sickle cell disease (SCD) do not have access to curative therapies, the availability of drug therapies that can modify disease severity remains highly desirable. Despite an increased understanding of the pathophysiology of SCD, only four drugs are approved by the US Food and Drug Administration. Most drug trials in SCD have involved the use of acute pain episodes as the primary
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Optimizing Platelet Transfusion through a Personalized Deep Learning Risk Assessment System for Demand Management. Blood (IF 20.3) Pub Date : 2023-10-27 Merlin Engelke,Cynthia Sabrina Schmidt,Giulia Baldini,Vicky Parmar,René Hosch,Katarzyna Borys,Sven Koitka,Amin T Turki,Johannes Haubold,Peter A Horn,Felix Nensa
Platelet demand management (PDM) is a resource-consuming task for physicians and transfusion managers of large hospitals. Inpatient numbers and institutional standards play significant roles in PDM. However, reliance on these factors alone commonly results in platelet shortages. Using data from multiple sources, we developed, validated, tested, and implemented a patient-specific approach to support
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Reciprocal stabilization of coagulation factor XIII-A and -B subunits determines plasma FXIII concentration. Blood (IF 20.3) Pub Date : 2023-10-26 James R Byrnes,Taek K Lee,Sherif Sharaby,Robert A Campbell,Dre'Von Dobson,Lori A Holle,Michelle Luo,Kadri Kangro,Jonathon Homeister,Maria M Aleman,James P Luyendyk,Bryce A Kerlin,Julie B Dumond,Alisa S Wolberg
Transglutaminase factor (F)XIII is essential for hemostasis, wound healing, and pregnancy maintenance. Plasma FXIII is composed of A and B subunit dimers synthesized in cells of hematopoietic origin and hepatocytes, respectively. The subunits associate tightly in circulation as FXIII-A2B2. FXIII-B2 stabilizes the (pro)active site-containing FXIII-A subunits. Interestingly, people with genetic FXIII-A
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CAR T-cells and Time-Limited Ibrutinib as Treatment for Relapsed/Refractory Mantle Cell Lymphoma: Phase II TARMAC Study. Blood (IF 20.3) Pub Date : 2023-10-26 Adrian G Minson,Nada Hamad,Chan Y Cheah,Constantine S Tam,Piers Blombery,David A Westerman,David S Ritchie,Huw Morgan,Nicholas Holzwart,Stephen Lade,Mary Ann Anderson,Amit Khot,John F Seymour,Molly Robertson,Imogen Caldwell,Georgina Ryland,Javad Saghebi,Zahra Sabahi,Jing Xie,Rachel M Koldej,Michael Dickinson
CD19-directed chimeric antigen receptor T-cells achieve high response rates in patients with relapsed or refractory mantle cell lymphoma. However, their use is associated with significant toxicity, relapse is a concern, and their broad tractability is unclear. Pre-clinical and clinical data support a beneficial synergistic effect of ibrutinib on apheresis product fitness, CAR-T expansion and toxicity
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Anti-PF4 immunothrombosis without proximate heparin or adenovirus vector vaccine exposure. Blood (IF 20.3) Pub Date : 2023-10-26 Linda Schönborn,Olga Esteban,Jan Wesche,Paulina Dobosz,Marta Broto,Sara Rovira Puig,Jessica Fuhrmann,Raquel Torres,Josep Serra,Roser Llevadot,Marta Palicio,Jing Jing Wang,Tom Paul Gordon,Edelgard Lindhoff-Last,Till Hoffmann,Lorenzo Alberio,Florian Langer,Christian Boehme,Eugenia Biguzzi,Leonie Grosse,Matthias Endres,Thomas G Liman,Thomas Thiele,Theodore E Warkentin,Andreas Greinacher
Platelet-activating anti-platelet factor 4 (PF4)/heparin antibodies and anti-PF4 antibodies cause heparin-induced thrombocytopenia (HIT) and vaccine-induced immune thrombocytopenia and thrombosis (VITT), respectively. Diagnostic and treatment considerations differ somewhat between HIT and VITT. We identified patients with thrombocytopenia and thrombosis without proximate heparin exposure or adenovirus-based
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PF4 activates the c-Mpl-Jak2 pathway in platelets. Blood (IF 20.3) Pub Date : 2023-10-26 Richard John Buka,Samantha Jayne Montague,Luis A Moran,Eleyna M Martin,Alexandre Slater,Stephen P Watson,Phillip Lindsay Ross Nicolson
Platelet factor 4 (PF4) is an abundant chemokine that is released from platelet α-granules upon activation. PF4 is central to the pathophysiology of vaccine-induced immune thrombocytopenia and thrombosis (VITT) in which antibodies to PF4 form immune complexes with PF4, which activate platelets and neutrophils through Fc receptors. In this study, we show that PF4 binds and activates the thrombopoietin
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T/myeloid MPAL with biallelic CEBPA mutations. Blood (IF 20.3) Pub Date : 2023-10-26 Mojgan Zarif,Hong Chang
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Hemostasis without clot formation: how platelets guard the vasculature in inflammation, infection, and malignancy. Blood (IF 20.3) Pub Date : 2023-10-26 Rainer Kaiser,Raphael Escaig,Leo Nicolai
Platelets are key vascular effectors in hemostasis, with activation signals leading to fast recruitment, aggregation, and clot formation. The canonical process of hemostasis is well-characterized and shares many similarities with pathological thrombus formation. However, platelets are also crucially involved in the maintenance of vascular integrity under both steady-state and inflammatory conditions
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Identifying STRN3-RARA as a new fusion gene for acute promyelocytic leukemia. Blood (IF 20.3) Pub Date : 2023-10-26 Qi Zhang,He Li,Xuelan Chen,Fan Gu,Lanxin Zhang,Lu Zhang,Tong Chen,Qiang Chen,Wentong Meng,Yu Wu,Hong Chang,Ting Liu,Chong Chen,Hongbing Ma,Yu Liu
Here we report a new fusion gene, STRN3-RARA, in acute promyelocytic leukemia (APL). It cooperates with UTX deficiency to drive full-blown APL in mice. Although STRN3-RARA leukemia quickly relapses after all-trans retinoic acid treatment, it can be restrained by cepharanthine.
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Genome-wide transcription factor-binding maps reveal cell-specific changes in the regulatory architecture of human HSPCs. Blood (IF 20.3) Pub Date : 2023-10-26 Shruthi Subramanian,Julie A I Thoms,Yizhou Huang,Paola Cornejo-Páramo,Forrest C Koch,Sebastien Jacquelin,Sylvie Shen,Emma Song,Swapna Joshi,Chris Brownlee,Petter S Woll,Diego Chacon-Fajardo,Dominik Beck,David J Curtis,Kenneth Yehson,Vicki Antonenas,Tracey O'Brien,Annette Trickett,Jason A Powell,Ian D Lewis,Stuart M Pitson,Maher K Gandhi,Steven W Lane,Fatemeh Vafaee,Emily S Wong,Berthold Göttgens,Hamid
Hematopoietic stem and progenitor cells (HSPCs) rely on a complex interplay among transcription factors (TFs) to regulate differentiation into mature blood cells. A heptad of TFs (FLI1, ERG, GATA2, RUNX1, TAL1, LYL1, LMO2) bind regulatory elements in bulk CD34+ HSPCs. However, whether specific heptad-TF combinations have distinct roles in regulating hematopoietic differentiation remains unknown. We
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Phase II Study of Inotuzumab Ozogamicin for Measurable Residual Disease in Acute Lymphoblastic Leukemia in Remission. Blood (IF 20.3) Pub Date : 2023-10-25 Elias J Jabbour,Fadi G Haddad,Nicholas J Short,Jayastu Senapati,Nitin Jain,Koji Sasaki,Jeffrey L Jorgensen,Sa A Wang,Yesid Alvarado,Xuemei Wang,Courtney D DiNardo,Lucia Masarova,Tapan M Kadia,Rebecca Garris,Farhad Ravandi,Hagop M Kantarjian
The detection of measurable residual disease (MRD) is the strongest predictor of relapse in acute lymphoblastic leukemia (ALL). Using inotuzumab ozogamicin in the setting of MRD may improve outcomes. Patients with ALL in first complete remission (CR1) or beyond (CR2+) with MRD ≥1x10-4 were enrolled in this phase II trial. Inotuzumab was administered at 0.6 mg/m2 on Day 1 and 0.3 mg/m2 on Day 8 of cycle
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CD19 occupancy with tafasitamab increases therapeutic index of CART19 cell therapy and diminishes severity of CRS. Blood (IF 20.3) Pub Date : 2023-10-25 R Leo Sakemura,Claudia Manriquez Roman,Paulina Horvei,Elizabeth L Siegler,James H Girsch,Olivia L Sirpilla,Carli M Stewart,Kun Yun,Ismail Can,Ekene J Ogbodo,Mohamad M Adada,Evandro Bezerra,Lionel Aurelien Kankeu Fonkoua,Mehrdad Hefazi,Michael W Ruff,Brooke L Kimball,Long K Mai,Truc N Huynh,Wendy Nevala,Kristina Ilieva,Christian Augsberger,Maria Patra-Kneuer,Jürgen Schanzer,Jan Endell,Christina Heitmüller
In the development of various strategies of anti-CD19 immunotherapy for treatment of B-cell malignancies, it remains unclear whether CD19 monoclonal antibody therapy impairs subsequent CD19-targeted chimeric antigen receptor T-cell (CART19) therapy. We evaluated the potential interference between the CD19-targeting monoclonal antibody tafasitamab and CART19 treatment in preclinical models. Concomitant
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The bone marrow is the primary site of thrombopoiesis. Blood (IF 20.3) Pub Date : 2023-10-25 Nathan L Asquith,Estelle Carminita,Virginia Camacho,Antonio Rodriguez-Romera,David Stegner,Daniela Freire,Isabelle C Becker,Kellie R Machlus,Abdullah Khan,Joseph E Italiano
Megakaryocytes generate thousands of platelets over their lifespan. More recently, roles in infection and inflammation have been reported. These findings have driven a study of extra-medullary thrombopoiesis, and megakaryocytes have been increasingly reported within the spleen and lung. However, the relative abundance of megakaryocytes in these organs compared to the bone marrow and the scale of their
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Three-Year Follow-Up Analysis of Axicabtagene Ciloleucel in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma (ZUMA-5). Blood (IF 20.3) Pub Date : 2023-10-25 Sattva S Neelapu,Julio C Chavez,Alison Sehgal,Narendranath Epperla,Matthew L Ulrickson,Emmanuel Bachy,Pashna Munshi,Carla Casulo,David G Maloney,Sven de Vos,Ran Reshef,Lori A Leslie,Olalekan O Oluwole,Ibrahim Yakoubagha,Rashmi Khanal,Joseph D Rosenblatt,Ronald Korn,Weixing Peng,Christine Lui,Jacob Wullf,Rhine R Shen,Soumya Poddar,A Scott Jung,Harry Miao,Sara Beygi,Caron A Jacobson
Axicabtagene ciloleucel (axi-cel) is an autologous anti-CD19 CAR T-cell therapy approved for relapsed/refractory (R/R) follicular lymphoma (FL). Approval was supported by the phase 2, multicenter, single-arm ZUMA-5 study of axi-cel in patients with R/R indolent non-Hodgkin lymphoma (iNHL; N=104), including FL and marginal zone lymphoma (MZL). In the primary analysis (17.5 months median follow-up),
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Clinical decision‐making and treatment of myelodysplastic syndromes Blood (IF 20.3) Pub Date : 2023-10-24 Eva S Hellstrom-Lindberg,Nicolaus Kröger
The myelodysplastic syndromes (MDS) constitute a profoundly heterogeneous myeloid malignancy with a common origin in the hemopoietic stem cell compartment. Consequently, patient management and treatment are as heterogeneous. Decision-making includes identifying risk, symptoms, and options for the individual patient and to make a risk-benefit analysis. The only potential cure is allogeneic stem cell
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EPIDEMIOLOGY AND GEOGRAPHIC CLUSTERING OF ERDHEIM-CHESTER DISEASE IN ITALY AND FRANCE. Blood (IF 20.3) Pub Date : 2023-10-23 Francesco Peyronel,Julien Haroche,Corrado Campochiaro,Francesco Pegoraro,Zahir Amoura,Alessandro Tomelleri,Martina Mazzariol,Matthias Papo,Giulio Cavalli,Giuseppe Daniele Benigno,Paride Fenaroli,Chrysanthos Grigoratos,Maria Cecilia Mengoli,Arturo Bonometti,Emilio Berti,Gustavo Savino,Mauro Cives,Iria Neri,Gaetano Pacinella,Antonino Tuttolomondo,Massimo Marano,Francesco Muratore,Andreina Manfredi,Alessandro
In this geo-epidemiological study performed in Italy-France, Erdheim-Chester disease (ECD) is increasingly diagnosed in the past few years and cases cluster in specific geographic areas, namely Southern Italy and Central France. Disease frequency inversely correlates with the Human Development Index.
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Tissue-infiltrating Alloreactive T Cells Require Id3 to Deflect PD-1-mediated Immune Suppression during GVHD. Blood (IF 20.3) Pub Date : 2023-10-23 Ying Wang,Shan He,Gennaro Calendo,Tien Bui,Yuanyuan Tian,Che Young Lee,Yan Zhou,Xin Zhao,Ciril Abraham,Wenbin Mo,Mimi Chen,Ruqayyah Sanders-Braggs,Jozef Madzo,Jean-Pierre J Issa,Elizabeth O Hexner,David L Wiest,Ran Reshef,Hai-Hui Xue,Yi Zhang
Persisting alloreactive donor T cells in target tissues are a determinant of graft-versus-host disease (GVHD), but the transcriptional regulators that control the persistence and function of tissue-infiltrating T cells remain elusive. We demonstrate here that Id3, a DNA-binding inhibitor, is critical for sustaining T cell responses in GVHD target tissues in mice, including the liver and intestine.
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Giroctocogene fitelparvovec gene therapy for severe hemophilia A: 104-week analysis of the Phase 1/2 Alta study. Blood (IF 20.3) Pub Date : 2023-10-23 Andrew D Leavitt,Barbara A Konkle,Kimo C Stine,Nathan Visweshwar,Thomas Harrington,Steven Arkin,Annie Fang,Frank Plonski,Anne Yver,Florence Ganne,Delphine Agathon,Maria de Los Angeles Resa,Li-Jung Tseng,Gregory Di Russo,Bettina M Cockroft,Liching Cao,Jeremy Rupon
Patients with hemophilia A require exogenous factor VIII (FVIII) or non-factor hemostatic agents to prevent spontaneous bleeding events. Adeno-associated virus (AAV) vector-based gene therapy is under clinical investigation to enable endogenous FVIII production. Giroctocogene fitelparvovec is a recombinant AAV serotype 6 vector containing the coding sequence for the B-domain-deleted human F8 gene.
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Narrowing the knowledge gap in atypical HUS. Blood (IF 20.3) Pub Date : 2023-10-19 Nicole C A J van de Kar,Jack F M Wetzels
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Tackling PD1i resistance in Hodgkin lymphoma. Blood (IF 20.3) Pub Date : 2023-10-19 Graham P Collins
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Gut microbiota diversity before allogeneic hematopoietic stem cell transplantation as a predictor of mortality in children. Blood (IF 20.3) Pub Date : 2023-10-19 Riccardo Masetti,Davide Leardini,Edoardo Muratore,Marco Fabbrini,Federica D'Amico,Daniele Zama,Francesco Baccelli,Francesca Gottardi,Tamara Belotti,Marek Ussowicz,Jowita Fraczkiewicz,Simone Cesaro,Marco Zecca,Pietro Merli,Marco Candela,Andrea Pession,Franco Locatelli,Arcangelo Prete,Patrizia Brigidi,Silvia Turroni
The correlation existing between gut microbiota diversity and survival after allogeneic hematopoietic stem cell transplantation (allo-HSCT) has so far been studied in adults. Pediatric studies question whether this association applies to children as well. Stool samples from a multicenter cohort of 90 pediatric allo-HSCT recipients were analyzed using 16S ribosomal RNA amplicon sequencing to profile
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Masqueraded mastocytosis with prominent crystal-storing histiocytic infiltration. Blood (IF 20.3) Pub Date : 2023-10-19 Kennosuke Karube,Kengo Takeuchi
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A new frontier for R-CHOP: is two better than one? Blood (IF 20.3) Pub Date : 2023-10-19 Umberto Vitolo,Annalisa Chiappella
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Macrophage heterogeneity in the single-cell era: facts and artifacts. Blood (IF 20.3) Pub Date : 2023-10-19 David A Hume,Susan M Millard,Allison R Pettit
In this spotlight, we review technical issues that compromise single-cell analysis of tissue macrophages, including limited and unrepresentative yields, fragmentation and generation of remnants, and activation during tissue disaggregation. These issues may lead to a misleading definition of subpopulations of macrophages and the expression of macrophage-specific transcripts by unrelated cells. Recognition
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Genetic drivers in the natural history of chronic lymphocytic leukemia development as early as 16 years before diagnosis. Blood (IF 20.3) Pub Date : 2023-10-19 P Martijn Kolijn,Florentin Späth,Mouhamad Khouja,Paul J Hengeveld,Lina van der Straten,Nikos Darzentas,Magnus Hultdin,James D McKay,Christiane Pott,Roel C H Vermeulen,Anton W Langerak
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Epstein-Barr virus encoded EBNA2 downregulates ICOSL by inducing miR-24 in B-cell lymphoma. Blood (IF 20.3) Pub Date : 2023-10-17 Martina Leopizzi,Lucia Mundo,Elena Messina,Federica Campolo,Stefano Lazzi,Antonio Angeloni,Cinzia Marchese,Lorenzo Leoncini,Carla Giordano,Frank Slack,Pankaj Trivedi,Eleni Anastasiadou
Hematological malignancies like Burkitt lymphoma (BL), Hodgkin's lymphoma (HL) and diffuse large B cell lymphoma (DLBCL) cause significant morbidity in humans. A substantial number of these lymphomas, particularly, HL and DLBCLs have poorer prognosis due to their association with Epstein-Barr virus (EBV). Our earlier studies have shown that EBV encoded nuclear antigen EBNA2 upregulates PD-L1 in DLBCL
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Mice expressing nonpolymerizable fibrinogen have reduced arterial and venous thrombosis with preserved hemostasis. Blood (IF 20.3) Pub Date : 2023-10-13 Woosuk Steve Hur,Tomohiro Kawano,Jean Marie N Mwiza,David S Paul,Robert H Lee,Emily G Clark,Emma G Bouck,Ananya Dutta,Can Cai,Stephen R Baker,Martin Guthold,Nigel Mackman,Pierre H Mangin,Alisa S Wolberg,Wolfgang Bergmeier,Matthew J Flick
Elevated circulating fibrinogen correlates with increased risk for both cardiovascular and venous thromboembolic diseases. In vitro studies show that formation of a highly dense fibrin matrix is a major determinant of clot structure and stability. Here, we analyzed the impact of nonpolymerizable fibrinogen on arterial and venous thrombosis as well as hemostasis in vivo using FgaEK mice that express
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The Influence of Immunodeficiency, Disease Features and Patient Characteristics on Survival in Plasmablastic Lymphoma. Blood (IF 20.3) Pub Date : 2023-10-13 Pietro R Di Ciaccio,Mark N Polizzotto,Kate Cwynarski,Alina S Gerrie,Catherine Burton,Mark Bower,John Kuruvilla,Silvia Montoto,Pamela McKay,Christopher P Fox,Samuel Milliken,Awachana Jiamsakul,Wendy Osborne,Graham P Collins,Kate Manos,Kim M Linton,Sunil Iyengar,Shireen Kassam,Michelle Poon Limei,David S Kliman,Nicole Wong Doo,Anne-Marie Watson,Pasquale Fedele,Costas K Yannakou,Stewart Hunt,Matthew Ku
Plasmablastic lymphoma (PBL) is a rare and aggressive non-Hodgkin lymphoma associated with immunodeficiency, characterized by uncertain treatment approaches and an unfavourable prognosis. We conducted a multicenter, international, retrospective cohort study, aiming to characterize the clinical features, risk factors, and outcomes of patients with PBL. Data were collected from 22 institutions across
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CAR Traffic jam: who can use the fast lane? Blood (IF 20.3) Pub Date : 2023-10-12 M T Kuipers,M J Kersten
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Blocked addiction to IL-15 for treating T-LGLL. Blood (IF 20.3) Pub Date : 2023-10-12 H Miles Prince
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Chronic Active Epstein-Barr Virus Disease Originates from Infected Hematopoietic Stem Cells. Blood (IF 20.3) Pub Date : 2023-10-12 Jingshi Wang,Min Su,Na Wei,Huanyu Yan,Jia Zhang,Yi Gong,Lin Wu,Dina Suolitiken,Yubo Pi,Deli Song,Leilei Chen,Huan Liu,Shuo Yang,Xi Wang,Zhao Wang
Chronic active Epstein-Barr Virus (EBV) disease (CAEBV) is lethal syndrome due to persistent EBV infection. When diagnosed as CAEBV, EBV infection was observed in multiple hematopoietic lineages, but the etiology of CAEBV is still elusive. Bone marrow and peripheral cells derived from five CAEBV patients, one EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH) patient, and two healthy controls
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Ibrutinib-based therapy reinvigorates CD8 T cells compared to chemoimmunotherapy: immune-monitoring from the E1912 trial. Blood (IF 20.3) Pub Date : 2023-10-12 Despoina Papazoglou,Victoria Wang,Tait D Shanafelt,Connie Lesnick,Nikolaos Ioannou,Giulia De Rossi,Sylvia Herter,Marina Bacac,Christian Klein,Martin S Tallman,Neil E Kay,Alan G Ramsay
Bruton's tyrosine kinase Inhibitors (BTKis) that target B cell receptor signaling have led to a paradigm shift in CLL treatment. BTKis have been shown to reduce abnormally high CLL-associated T cell counts and the expression of immune checkpoint receptors concomitantly with tumor reduction. However, the impact of BTKi therapy on T cell function has not been fully characterized. Here, we performed longitudinal
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BMP5: a novel tile of the hepcidin regulatory pathway. Blood (IF 20.3) Pub Date : 2023-10-12 Antonella Nai
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BMP5 contributes to hepcidin regulation and systemic iron homeostasis in mice. Blood (IF 20.3) Pub Date : 2023-10-12 Xia Xiao,Yang Xu,Gillian A Moschetta,Yang Yu,Allison L Fisher,Víctor M Alfaro-Magallanes,Shasta McMillen,Sydney Phillips,Chia-Yu Wang,Jan Christian,Jodie L Babitt
Hepcidin is the master regulator of systemic iron homeostasis. The bone morphogenetic protein (BMP) signaling pathway is a critical regulator of hepcidin expression in response to iron and erythropoietic drive. Although endothelial-derived BMP6 and BMP2 ligands have key functional roles as endogenous hepcidin regulators, both iron and erythropoietic drives still regulate hepcidin in mice lacking either
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Complement activation drives Transfusion-related acute lung injury via macrophage trafficking and formation of NETs. Blood (IF 20.3) Pub Date : 2023-10-06 Saskia van der Velden,Thijs L J van Osch,Amina Seghier,Arthur Bentlage,Juk Yee Mok,Dionne M Geerdes,Wim Je van Esch,Richard Pouw,Mieke C Brouwer,Ilse Jongerius,Masja de Haas,Leendert Porcelijn,C Ellen van der van der Schoot,Gestur Vidarsson,Rick Kapur
Transfusion-related acute lung injury (TRALI) is one of the leading causes of transfusion-related fatalities and to date, without available therapies. Here we investigated the role of the complement system in TRALI. Murine anti-major histocompatibility complex (MHC) class I antibodies were used in TRALI mouse-models, in combination with analyses of TRALI patient plasma samples. We found that in vitro