-
Systemic mastocytosis: dying or survivin Blood (IF 20.3) Pub Date : 2024-03-14 Joakim S. Dahlin, Gunnar Nilsson
-
-
A road map of relapse in MDS after allo-HSCT Blood (IF 20.3) Pub Date : 2024-03-14 Juan Jose Rodriguez-Sevilla, Simona Colla
-
Hemolysis impairs sickle cell erythropoiesis Blood (IF 20.3) Pub Date : 2024-03-14 Constance T. Noguchi
-
Monomorphic epitheliotropic T-cell lymphoma with strong CD4 expression Blood (IF 20.3) Pub Date : 2024-03-14 Siba El Hussein
-
-
MRD at the End of Induction and EFS in T-cell Lymphoblastic Lymphoma: Children’s Oncology Group Trial AALL1231. Blood (IF 20.3) Pub Date : 2024-03-13 Robert J. Hayashi, Michelle L. Hermiston, Brent L. Wood, David T. Teachey, Meenakshi Devidas, Zhiguo Chen, Robert D. Annett, Barbara L. Asselin, Keith August, Steve Cho, Kimberly P. Dunsmore, Jason Lawrence Freedman, Paul J. Galardy, Paul Harker-Murray, Terzah M. Horton, Alok I. Jaju, Allison Lam, Yoav H. Messinger, Rodney R. Miles, Maki Okada, Samir Patel, Eric S. Schafer, Tai Schechter, Kristin A
Defining prognostic variables in T-lymphoblastic lymphoma (T-LL) remains a challenge. AALL1231 was a COG phase 3 clinical trial for newly diagnosed with T Acute Lymphoblastic leukemia or T-LL patients randomizing children and young adults to a modified augmented BFM backbone to receive standard therapy (Arm A) or with addition of bortezomib (Arm B). Optional bone marrow (BM) samples to assess minimal
-
In vivo ablation of NFκB cascade effectors alleviates disease burden in myeloproliferative neoplasms Blood (IF 20.3) Pub Date : 2024-03-12 Angelo B. A. Laranjeira, Tim Kong, Steven C. Snyder, Mary C. Fulbright, Daniel A. C. Fisher, Daniel T. Starczynowski, Stephen T. Oh
Hyperactivation of the NFκB cascade propagates oncogenic signaling and pro-inflammation, which together augments disease burden in myeloproliferative neoplasms (MPNs). Here, we systematically ablate NFκB signaling effectors to identify core dependencies using a series of primary samples and syngeneic and patient-derived xenograft (PDX) mouse models. Conditional knockout of attenuated and -driven onset
-
DNA damage response defects in hematologic malignancies: mechanistic insights and therapeutic strategies Blood (IF 20.3) Pub Date : 2024-03-12 Marwan Kwok, Angelo Agathanggelou, Tatjana Stankovic
The DNA damage response (DDR) encompasses the detection and repair of DNA lesions and is fundamental to the maintenance of genome integrity. Germline DDR alterations underlie hereditary chromosome instability syndromes by promoting the acquisition of pathogenic structural variants in hematopoietic cells, resulting in increased predisposition to hematologic malignancies. Also frequent in hematologic
-
Nilotinib with or without cytarabine for Philadelphia positive acute lymphoblastic leukemia. Blood (IF 20.3) Pub Date : 2024-03-12 Yves Chalandon, Philippe Rousselot, Sylvie Chevret, Jean-Michel Cayuela, Rathana Kim, Françoise Huguet, Patrice Chevallier, Carlos Graux, Anne Thiebaut-Bertrand, Sylvain Chantepie, Xavier Thomas, Laure Vincent, Céline Berthon, Yosr Hicheri, Emmanuel Raffoux, Martine Escoffre-Barbe, Isabelle Plantier, Magalie Joris, Pascal Turlure, Florence Pasquier, Amine Belhabri, Gabrielle Roth Guepin, Sabine Blum
We previously demonstrated that a reduced-intensity chemotherapy schedule can safely replace Hyper-CVAD cycle 1 when combined with imatinib in adults with Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL). In the present randomized GRAAPH-2014 trial, we used nilotinib and addressed the omission of cytarabine (Ara-C) in consolidation. The primary objective was the major molecular response
-
Epigenetic control over cell-intrinsic immune response antagonizes self-renewal in acute myeloid leukemia Blood (IF 20.3) Pub Date : 2024-03-11 Eloísa Felipe Fumero, Carolin Walter, Joris Maximillian Frenz, Franca Seifert, Vijay Alla, Thorben Henning, Linus Angenendt, Wolfgang Hartmann, Sebastian Wolf, Hubert Serve, Thomas Oellerich, Georg Lenz, Carsten Müller-Tidow, Christoph Schliemann, Otmar Huber, Martin Dugas, Matthias Mann, Ashok Kumar Jayavelu, Jan-Henrik Mikesch, Maria Francisca Arteaga
The histone demethylase PHF8 is a master regulator of cell-intrinsic immune response in acute myeloid leukemia.
-
T cell help in the tumor microenvironment enhances rituximab-mediated NK cell ADCC Blood (IF 20.3) Pub Date : 2024-03-11 Jyoti Arora, Sabarish Ayyappan, Chaobo Yin, Brian J. Smith, Caitlin D. Lemke-Miltner, Zhaoming Wang, Umar Farooq, George J. Weiner
Rituximab (RTX) and other monoclonal antibodies (mAbs) that bind directly to malignant cells are of great clinical value but are not effective for all patients. A major mechanism of action of RTX is antibody dependent cellular cytotoxicity (ADCC) mediated by NK cells. Prior in vitro studies in our laboratory demonstrated that T cells contribute to maintaining the viability and cytotoxic potential of
-
IDH Mutant Myeloid Neoplasms are Associated with Seronegative Rheumatoid Arthritis and Innate Immune Activation Blood (IF 20.3) Pub Date : 2024-03-11 Lih En Hong, Mihir D Wechalekar, Monika Kutyna, Annabelle Small, Kelly Lim, Chloe Thompson-Peach, Joule J Li, Rakchha Chhetri, Hamish S Scott, Anna Brown, Christopher N Hahn, David T Yeung, Salvia Sajid, Nirmal Robinson, Ranjeny Thomas, Susan Branford, Richard J D’Andrea, Saumya E Samaraweera, Mrinal Patnaik, Susanna Proudman, Daniel Thomas, Chung Hoow Kok, Mithun V Shah, Devendra K Hiwase
High prevalence of -mutations in seronegative rheumatoid arthritis (RA) with myeloid neoplasm, elevated 2-hydroxyglutarate, dysregulated innate immunity and pro-inflammatory microenvironment, suggests causative association between -mutations and seronegative RA. Our findings merit investigation of IDH-inhibitors as therapeutics for seronegative IDH-mutated RA.
-
Hemoglobin Bart’s Hydrops Fetalis: Charting the Past and Envisioning the Future Blood (IF 20.3) Pub Date : 2024-03-11 Ali Amid, Siyu Liu, Christian Babbs, Douglas R. Higgs
Hemoglobin Bart’s hydrops fetalis syndrome (BHFS) represents the most severe form of α-thalassemia, arising from deletion of the duplicated α-globin genes from both alleles. The absence of α-globin leads to the formation of non-functional hemoglobin Bart’s (γ) or hemoglobin H (HbH: β) resulting in severe anemia, tissue hypoxia, and, in some cases, variable congenital or neurocognitive abnormalities
-
Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis (ATLAS-PPX) Blood (IF 20.3) Pub Date : 2024-03-11 Gili Kenet, Beatrice Nolan, Bulent Zulfikar, Bulent Antmen, Peter Kampmann, Tadashi Matsushita, Chur-Woo You, Kateryna Vilchevska, Catherine N. Bagot, Azizan Sharif, Flora Peyvandi, Guy Young, Claude Negrier, Jiarui Chi, Barbara Kittner, Christian Sussebach, Fadi Shammas, Baisong Mei, Shauna Andersson, Kaan Kavakli.
Fitusiran, a subcutaneous (SC) investigational siRNA therapeutic, targets antithrombin to rebalance hemostasis in people with hemophilia A or B (PwHA/B), irrespective of inhibitor status. This Phase 3, open-label study (NCT03549871) evaluated the efficacy and safety of fitusiran prophylaxis in males aged ≥ 12 years with hemophilia A or B, with or without inhibitors, who received prior bypassing agent
-
Vector integration and fate in the hemophilia dog liver multi-years following AAV-FVIII gene transfer Blood (IF 20.3) Pub Date : 2024-03-11 Paul Batty, Sylvia Fong, Matteo Franco, Choong-Ryoul Sihn, Laura L. Swystun, Saira Afzal, Lorianne Harpell, David Hurlbut, Abbey Pender, Cheng Su, Hauke Thomsen, Christopher Wilson, Loubna Youssar, Andrew Winterborn, Irene Gil-Farina, David Lillicrap
Gene therapy using adeno-associated viral (AAV) vectors is a promising approach for the treatment of monogenic disorders. Long-term multi-year transgene expression has been demonstrated in animal models and clinical studies. Nevertheless, uncertainties remain concerning the nature of AAV vector persistence and whether there is a potential for genotoxicity. Here, we describe the mechanisms of AAV vector
-
Alloengraftment without significant toxicity or GVHD in CD45 antibody-drug conjugate conditioned Fanconi anemia mice Blood (IF 20.3) Pub Date : 2024-03-08 Asim Saha, Rahul Palchaudhuri, Leanne Lanieri, Sharon Hyzy, Megan J. Riddle, Jamie Panthera, Cindy R. Eide, Jakub Tolar, Angela Panoskaltsis-Mortari, Lev Gorfinkel, Victor Tkachev, Ulrike Gerdemann, Francesca Alvarez Calderon, Elisa Rojas Palato, Margaret L. MacMillan, John E. Wagner, Leslie S. Kean, Mark J. Osborn, Hans-Peter Kiem, David T. Scadden, Lisa M. Olson, Bruce R. Blazar
Fanconi anemia (FA) is an inherited DNA repair disorder characterized by bone marrow (BM) failure, developmental abnormalities, myelodysplasia, and leukemia and solid tumor predisposition. Allogeneic hematopoietic stem cell transplantation (allo-HSCT), a mainstay treatment, is limited by conditioning regimen-related toxicity and graft-versus-host disease (GVHD). Antibody-drug-conjugates (ADCs) targeting
-
Long noncoding RNA GATA2AS influences human erythropoiesis by transcription factor and chromatin landscape modulation Blood (IF 20.3) Pub Date : 2024-03-08 Guoyou Liu, Juhyun Kim, Nicole Nguyen, Lecong Zhou, Ann Dean
LncRNAs are extensively expressed in eukaryotic cells and have been revealed to be important for regulating cell differentiation. Many lncRNAs have been found to regulate erythroid differentiation in the mouse. However, given the low sequence conservation of lncRNAs between mouse and human, our understanding of lncRNAs in human erythroid differentiation remains incomplete. LncRNAs are often transcribed
-
Differential Effects of Itacitinib, Fedratinib, and Ruxolitinib in Mouse Models of Hemophagocytic Lymphohistiocytosis Blood (IF 20.3) Pub Date : 2024-03-08 Camille Keenan MD MPH, Sabrin Albeituni PhD, Ninad Oak PhD, Alexa Stroh MBA, Heather S. Tillman DVM PhD, Yingzhe Wang PhD, Burgess B. Freeman III PharmD, Silvia Aleman Arteaga, Lauren K. Meyer MD PhD, Rolanda Woods, Katherine C. Verbist PhD, Yinmei Zhou MS, Cheng Cheng PhD, Kim E. Nichols MD
Hemophagocytic lymphohistiocytosis (HLH) comprises a severe hyperinflammatory phenotype driven by the overproduction of cytokines, many of which signal via the JAK/STAT pathway. Indeed, the JAK1/2 inhibitor ruxolitinib has demonstrated efficacy in pre-clinical studies and early-phase clinical trials in HLH. Nevertheless, concerns remain for ruxolitinib-induced cytopenias, which are postulated to result
-
Circulating Hematopoietic Stem/Progenitor Cells subsets contribute to human hematopoietic homeostasis Blood (IF 20.3) Pub Date : 2024-03-08 Pamela Quaranta, Luca Basso-Ricci, Raisa Jofra Hernandez, Guido Pacini, Matteo Maria Naldini, Matteo Barcella, Luca Seffin, Giulia Pais, Giulio Spinozzi, Fabrizio Benedicenti, Carlo Pietrasanta, Jin-Gyu Cheong, Andrea Ronchi, Lorenza Pugni, Francesca Dionisio, Ilaria Monti, Stefania Giannelli, Silvia Darin, Federico Fraschetta, Graziano Barera, Francesca Ferrua, Valeria Calbi, Marco Ometti, Raffaella
In physiological conditions, few circulating hematopoietic stem/progenitor cells (cHSPC) are present in the peripheral blood but their contribution to hematopoietic homeostasis in humans remain unsolved. By integrating advanced immunophenotyping, cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), functional single-cell assays and integration site (IS) clonal tracking, we unveiled
-
Germline Genetic NBN Variation and Predisposition to B-cell Acute Lymphoblastic Leukemia in Children Blood (IF 20.3) Pub Date : 2024-03-08 Carolin Escherich MD, Wenan Chen PhD, Yizhen Li PhD, Wenjian Yang PhD, Rina Nishii PhD, Zhenhua Li PhD, Elizabeth A. Raetz MD, Meenakshi Devidas PhD, Gang Wu PhD, Kim E. Nichols MD, Hiroto Inaba MD, Ching-Hon Pui MD, Sima Jeha MD, Bruce M. Camitta MD, Eric Larsen MD, Stephen P. Hunger MD, Mignon L. Loh MD, Jun J. Yang PhD
Biallelic mutation in the DNA-damage repair gene is the genetic cause of Nijmegen Breakage Syndrome, which is associated with predisposition to lymphoid malignancies. Heterozygous carriers of germline variants may also be at risk for leukemia development, although this is much less characterized. Sequencing 4,325 pediatric B-ALL patients, we systematically examined the frequency of germline variants
-
Targeting the TNF/IAP pathway synergizes with anti-CD3 immunotherapy in T-Cell Acute Lymphoblastic Leukemia Blood (IF 20.3) Pub Date : 2024-03-06 Andrea Ávila Ávila, Kanokporn Nuantang, Mariana L. Oliveira, Sabine Druillennec, Benedetta Zaniboni, Etienne Lengliné, Vahid Asnafi, Jacques Ghysdael, Christine Tran Quang
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. Current treatments, based on intensive chemotherapy regimens provide overall survival rates of ∼85% in children and <50% in adults, calling the search of new therapeutic options. We previously reported that targeting the T cell receptor (TCR) in T-ALL with anti-CD3 (αCD3) mAbs enforces a molecular program akin to
-
Sickle cell disease iPSC-derived sensory neurons exhibit increased excitability and sensitization to patient plasma Blood (IF 20.3) Pub Date : 2024-03-05 Reilly L. Allison, Emily Welby, Vanessa Ehlers, Anthony Burand, Olena Isaeva, Damaris Nieves Torres, Janelle Highland, Amanda M. Brandow, Cheryl Stucky, Allison D. Ebert
Individuals living with sickle cell disease (SCD) experience severe recurrent acute and chronic pain. Challenges to gaining mechanistic insight into pathogenic SCD pain processes include differential gene expression and function of sensory neurons between humans and mice with SCD, and extremely limited availability of neuronal tissues from SCD patients. Here we used SCD patient-derived induced pluripotent
-
A potential mechanism for the cytoprotective effects of activated protein C–released endothelial extracellular vesicles Blood (IF 20.3) Pub Date : 2024-03-03 Kaushik Das, Shiva Keshava, Tanmoy Mukherjee, L. Vijaya Mohan Rao
Activated protein C (APC) was shown to release extracellular vesicles (EVs). APC bound to the EVs was thought to be responsible for cytoprotection. Our study demonstrates that the cytoprotective effects of APC-released EVs are independent of APC. APC-released EVs carry anti-inflammatory microRNAs in their cargo.
-
ctDNA improves prognostic prediction in relapsed/refractory MM receiving ixazomib, lenalidomide, and dexamethasone Blood (IF 20.3) Pub Date : 2024-03-03 Yasunori Kogure, Hiroshi Handa, Yuta Ito, Masaki Ri, Yuichi Horigome, Masaki Iino, Yoriko Harazaki, Takahiro Kobayashi, Masahiro Abe, Tadao Ishida, Shigeki Ito, Hiromi Iwasaki, Junya Kuroda, Hirohiko Shibayama, Kazutaka Sunami, Hiroyuki Takamatsu, Hideto Tamura, Toshiaki Hayashi, Kiwamu Akagi, Tomohiro Shinozaki, Takahiro Yoshida, Ikuo Mori, Shinsuke Iida, Takahiro Maeda, Keisuke Kataoka
It remains elusive how driver mutations, including those detected in circulating tumor DNA (ctDNA), affect prognosis in relapsed/refractory multiple myeloma (RRMM). Here we performed targeted-capture sequencing using bone marrow plasma cells (BMPC) and ctDNA of 261 RRMM cases uniformly treated with ixazomib, lenalidomide, and dexamethasone in a multicenter, prospective, observational study. We detected
-
Smoldering multiple myeloma: taking the narrow over the wide path? Blood (IF 20.3) Pub Date : 2024-03-03 Herve Avet-Loiseau, Nizar J. Bahlis
-
Expanding the repertoire reveals recurrent, cryptic, and hematopoietic HLA class I minor histocompatibility antigens Blood (IF 20.3) Pub Date : 2024-03-03 Kyra J. Fuchs, Marian van de Meent, M. Willy Honders, Indu Khatri, Michel G. D. Kester, Eva A. S. Koster, Georgia Koutsoumpli, Arnoud H. de Ru, Cornelis A. M. van Bergen, Peter A. van Veelen, Peter A. C. ’t Hoen, Peter van Balen, Erik B. van den Akker, J. Hendrik Veelken, Constantijn J. M. Halkes, J. H. Frederik Falkenburg, Marieke Griffioen
Allogeneic stem cell transplantation (alloSCT) is a curative treatment for hematological malignancies. After HLA-matched alloSCT, antitumor immunity is caused by donor T cells recognizing polymorphic peptides, designated minor histocompatibility antigens (MiHAs), that are presented by HLA on malignant patient cells. However, T cells often target MiHAs on healthy nonhematopoietic tissues of patients
-
Platelet dysfunction reversal with cold-stored vs room temperature–stored platelet transfusions Blood (IF 20.3) Pub Date : 2024-03-03 Valery J. Kogler, Jeffrey A. Miles, Tahsin Özpolat, S. Lawrence Bailey, Daire A. Byrne, Morgan Bawcom-Randall, Yi Wang, Hannah J. Larsen, Franklin Reed, Xiaoyun Fu, Moritz Stolla
Platelets are stored at room temperature for 5 to 7 days (room temperature–stored platelets [RSPs]). Because of frequent and severe shortages, the US Food and Drug Administration recently approved up to 14-day cold-stored platelets (CSPs) in plasma. However, the posttransfusion function of CSPs is unknown and it is unclear which donors are best suited to provide either RSPs or CSPs. In this study,
-
Daratumumab, carfilzomib, lenalidomide, and dexamethasone with tandem transplant for high-risk newly diagnosed myeloma Blood (IF 20.3) Pub Date : 2024-02-27 Cyrille Touzeau, Aurore Perrot, Cyrille Hulin, Salomon Manier, Margaret Macro, Marie-Lorraine Chretien, Lionel Karlin, Martine Escoffre, Caroline Jacquet, Mourad Tiab, Xavier Leleu, Hervé Avet-Loiseau, Alexandra Jobert, Lucie Planche, Jill Corre, Philippe Moreau
High-risk (HR) cytogenetics are associated with poor outcomes in newly diagnosed multiple myeloma (NDMM), and dedicated studies should address this difficult-to-treat population. The phase 2 study 2018-04 from the Intergroupe Francophone du Myelome evaluated feasibility of an intensive strategy with quadruplet induction and consolidation plus tandem transplant in HR transplant-eligible (TE) NDMM. HR
-
A CD38-directed, single-chain T-cell engager targets leukemia stem cells through IFN-γ–induced CD38 expression Blood (IF 20.3) Pub Date : 2024-02-26 Mariam Murtadha, Miso Park, Yinghui Zhu, Enrico Caserta, Ottavio Napolitano, Theophilus Tandoh, Milad Moloudizargari, Alex Pozhitkov, Mahmoud Singer, Ada Alice Dona, Hawa Vahed, Asaul Gonzalez, Kevin Ly, Ching Ouyang, James F. Sanchez, Lokesh Nigam, Amanda Duplan, Arnab Chowdhury, Lucy Ghoda, Ling Li, Bin Zhang, Amrita Krishnan, Guido Marcucci, John C. Williams, Flavia Pichiorri
Treatment resistance of leukemia stem cells (LSCs) and suppression of the autologous immune system represent major challenges to achieve a cure in acute myeloid leukemia (AML). Although AML blasts generally retain high levels of surface CD38 (CD38), LSCs are frequently enriched in the CD34CD38 blast fraction. Here, we report that interferon gamma (IFN-γ) reduces LSCs clonogenic activity and induces
-
Tyrosine kinase inhibitor response of ABL-class acute lymphoblastic leukemia: the role of kinase type and SH3 domain Blood (IF 20.3) Pub Date : 2024-02-26 Inge van Outersterp, Sarah K. Tasian, Caitlin E. J. Reichert, Aurélie Boeree, Hester A. de Groot-Kruseman, Gabriele Escherich, Judith M. Boer, Monique L. den Boer
Acute lymphoblastic leukemia (ALL) with fusion of ABL-class tyrosine kinase genes other than :: occurs in ∼3% of children with ALL. The tyrosine kinase genes involved in this ::-like (Ph-like) subtype include , , , and , each of which has up to 10 described partner genes. ABL-class ALL resembles ::-positive ALL with a similar gene expression profile, poor response to chemotherapy, and sensitivity to
-
CD155/PVR determines acute myeloid leukemia targeting by Delta One T cells Blood (IF 20.3) Pub Date : 2024-02-22 Sofia Mensurado, Carolina Condeço, Diego Sánchez-Martínez, Sara Shirley, Rui M. L. Coelho, Néstor Tirado, Meritxell Vinyoles, Rafael Blanco-Domínguez, Leandro Barros, Beatriz Galvão, Noélia Custódio, Maria Gomes da Silva, Pablo Menéndez, Bruno Silva-Santos
Relapsed or refractory acute myeloid leukemia (AML) remains a major therapeutic challenge. We have recently developed a Vδ1 γδ T cell–based product for adoptive immunotherapy, named Delta One T (DOT) cells, and demonstrated their cytolytic capacity to eliminate AML cell lines and primary blasts in vitro and in vivo. However, the molecular mechanisms responsible for the broad DOT-cell recognition of
-
Postinduction molecular MRD identifies patients with NPM1 AML who benefit from allogeneic transplant in first remission Blood (IF 20.3) Pub Date : 2024-02-18 Jad Othman, Nicola Potter, Adam Ivey, Jelena Jovanovic, Manohursingh Runglall, Sylvie D. Freeman, Amanda Gilkes, Ian Thomas, Sean Johnson, Joanna Canham, Jamie Cavenagh, Panagiotis Kottaridis, Claire Arnold, Hans Beier Ommen, Ulrik Malthe Overgaard, Mike Dennis, Alan Burnett, Charlotte Wilhelm-Benartzi, Richard Dillon, Nigel H. Russell
Selection of patients with -mutated acute myeloid leukemia (AML) for allogeneic transplant in first complete remission (CR1-allo) remains controversial because of a lack of robust data. Consequently, some centers consider baseline –internal tandem duplication (ITD) an indication for transplant, and others rely on measurable residual disease (MRD) status. Using prospective data from the United Kingdom
-
The influence of voxelotor on cerebral blood flow and oxygen extraction in pediatric sickle cell disease Blood (IF 20.3) Pub Date : 2024-02-18 Rowan O. Brothers, Katherine B. Turrentine, Mariam Akbar, Sydney Triplett, Hongting Zhao, Tara M. Urner, Adam Goldman-Yassen, Richard A. Jones, Jack Knight-Scott, Sarah S. Milla, Shasha Bai, Amy Tang, R. Clark Brown, Erin M. Buckley
Voxelotor is an inhibitor of sickle hemoglobin polymerization that is used to treat sickle cell disease. Although voxelotor has been shown to improve anemia, the clinical benefit on the brain remains to be determined. This study quantified the cerebral hemodynamic effects of voxelotor in children with sickle cell anemia (SCA) using noninvasive diffuse optical spectroscopies. Specifically, frequency-domain
-
Blood and guts: how the intestinal microbiome shapes hematopoiesis and treatment of hematologic disease Blood (IF 20.3) Pub Date : 2024-02-18 Josaura Fernandez Sanchez, Arushana Ali Maknojia, Katherine Y. King
[Display omitted]
-
How I treat ETP-ALL in children Blood (IF 20.3) Pub Date : 2024-02-18 Ryan J. Summers, David T. Teachey, Stephen P. Hunger
[Display omitted]
-
Cryo-EM structure and functional basis of prothrombin recognition by a type I anti-prothrombin antiphospholipid antibody Blood (IF 20.3) Pub Date : 2024-02-18 Suresh Kumar, Brock Summers, Kathrine Basore, Vittorio Pengo, Robert Flaumenhaft, Nicola Pozzi
Anti-prothrombin antibodies are found in antiphospholipid patients, but how they interact with prothrombin remains elusive. Prothrombin adopts closed and open forms. We recently discovered type I and type II antibodies and proposed that type I recognizes the open form. In this study, we report the discovery and structural and functional characterization in human plasma of a type I antibody, POmAb (Prothrombin
-
BRG1/BRM inhibitor targets AML stem cells and exerts superior preclinical efficacy combined with BET or menin inhibitor Blood (IF 20.3) Pub Date : 2024-02-18 Warren Fiskus, Jessica Piel, Mike Collins, Murphy Hentemann, Branko Cuglievan, Christopher P. Mill, Christine E. Birdwell, Kaberi Das, John A. Davis, Hanxi Hou, Antrix Jain, Anna Malovannaya, Tapan M. Kadia, Naval Daver, Koji Sasaki, Koichi Takahashi, Danielle Hammond, Patrick K. Reville, Jian Wang, Sanam Loghavi, Rwik Sen, Xinjia Ruan, Xiaoping Su, Lauren B. Flores, Courtney D. DiNardo, Kapil N. Bhalla
BRG1 (SMARCA4) and BRM (SMARCA2) are the mutually exclusive core ATPases of the chromatin remodeling BAF (BRG1/BRM-associated factor) complexes. They enable transcription factors/cofactors to access enhancers/promoter and modulate gene expressions responsible for cell growth and differentiation of acute myeloid leukemia (AML) stem/progenitor cells. In AML with MLL1 rearrangement (MLL1r) or mutant NPM1
-
Current and upcoming treatment approaches to common subtypes of PTCL (PTCL NOS, ALCL, and TFHs) Blood (IF 20.3) Pub Date : 2024-02-04 Alison J. Moskowitz, Robert N. Stuver, Steven M. Horwitz
[Display omitted]
-
How I reduce and treat posttransplant relapse of MDS Blood (IF 20.3) Pub Date : 2024-02-04 Alain Mina, Peter L. Greenberg, H. Joachim Deeg
[Display omitted]
-
Diagnosis, prognostic factors, and assessment of ALL in adults: 2024 ELN recommendations from a European expert panel Blood (IF 20.3) Pub Date : 2024-02-02 Nicola Gökbuget, Nicolas Boissel, Sabina Chiaretti, Herve Dombret, Michael Doubek, Adele Fielding, Robin Foa, Sebastian Giebel, Dieter Hoelzer, Mathilde Hunault, David I. Marks, Giovanni Martinelli, Oliver Ottmann, Anita Rijneveld, Philippe Rousselot, Josep Ribera, Renato Bassan
-
Regulatory T cells suppress myeloma-specific immunity during autologous stem cell mobilization and transplantation Blood (IF 20.3) Pub Date : 2024-02-02 Shuichiro Takahashi, Simone A. Minnie, Kathleen S. Ensbey, Christine R. Schmidt, Tomoko Sekiguchi, Samuel R. W. Legg, Ping Zhang, Motoko Koyama, Stuart D. Olver, Alika D. Collinge, Sara Keshmiri, Melissa L. Comstock, Antiopi Varelias, Damian J. Green, Geoffrey R. Hill
Autologous stem cell transplantation (ASCT) is the standard of care consolidation therapy for eligible patients with myeloma but most patients eventually progress, an event associated with features of immune escape. Novel approaches to enhance antimyeloma immunity after ASCT represent a major unmet need. Here, we demonstrate that patient-mobilized stem cell grafts contain high numbers of effector CD8
-
Plasmin-cleaved von Willebrand factor as a biomarker for microvascular thrombosis Blood (IF 20.3) Pub Date : 2024-01-30 Hinde El Otmani, Rowan Frunt, Simone Smits, Arjan D. Barendrecht, Steven de Maat, Rob Fijnheer, Peter J. Lenting, Claudia Tersteeg
von Willebrand factor (VWF) is an essential contributor to microvascular thrombosis. Physiological cleavage by ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) limits its prothrombotic properties, explaining why ADAMTS13 deficiency leads to attacks of microthrombosis in patients with thrombotic thrombocytopenic purpura (TTP). We previously reported that plasminogen
-
PI3Kγ maintains the self-renewal of acute myeloid leukemia stem cells by regulating the pentose phosphate pathway Blood (IF 20.3) Pub Date : 2024-01-28 Hao Gu, Chiqi Chen, Zhi-Shuai Hou, Xia-Di He, Shaozhen Xie, Jing Ni, Changli Qian, Xin Cheng, Tao Jiang, Ce Yang, Thomas M. Roberts, Junke Zheng, Judith A. Varner, Scott A. Armstrong, Jean J. Zhao
Acute myeloid leukemia (AML) is an aggressive hematological malignancy originating from transformed hematopoietic stem or progenitor cells. AML prognosis remains poor owing to resistance and relapse driven by leukemia stem cells (LSCs). Targeting molecules essential for LSC function is a promising therapeutic approach. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway is often dysregulated in AML
-
Targeting IDH2R140Q and other neoantigens in acute myeloid leukemia Blood (IF 20.3) Pub Date : 2024-01-22 Wingchi K. Leung, Alejandro G. Torres Chavez, Matthew French-Kim, Paul Shafer, Maksim Mamonkin, LaQuisa C. Hill, Manik Kuvalekar, Yovana Velazquez, Ayumi Watanabe, Norihiro Watanabe, Valentina Hoyos, Premal Lulla, Ann M. Leen
For patients with high-risk or relapsed/refractory acute myeloid leukemia (AML), allogeneic stem cell transplantation (allo-HSCT) and the graft-versus-leukemia effect mediated by donor T cells, offer the best chance of long-term remission. However, the concurrent transfer of alloreactive T cells can lead to graft-versus-host disease that is associated with transplant-related morbidity and mortality
-
Low ectonucleotidase activity and increased neutrophil-platelet aggregates in patients with antiphospholipid syndrome Blood (IF 20.3) Pub Date : 2024-01-21 Somanathapura K. NaveenKumar, Ajay Tambralli, Bruna Mazetto Fonseca, Srilakshmi Yalavarthi, Wenying Liang, Claire K. Hoy, Cyrus Sarosh, Christine E. Rysenga, Caroline H. Ranger, Caroline E. Vance, Jacqueline A. Madison, Fernanda A. Orsi, Suman L. Sood, Jordan K. Schaefer, Yu Zuo, Jason S. Knight
Many patients with antiphospholipid syndrome had decreased ectonucleotidase activity on neutrophils and platelets, which enabled extracellular nucleotides to trigger neutrophil-platelet aggregates. This phenotype was replicated by treating healthy neutrophils and platelets with patient-derived antiphospholipid antibodies or ectonucleotidase inhibitors.
-
A randomized phase 2 trial of oral vitamin A for graft-versus-host disease in children and young adults Blood (IF 20.3) Pub Date : 2024-01-19 Pooja Khandelwal, Lucille Langenberg, Nathan Luebbering, Kelly E. Lake, Abigail Butcher, Kylie Bota, Kristie N. Ramos, Cynthia Taggart, Hannah Choe, Sumithira Vasu, Ashley Teusink-Cross, Jane Koo, Gregory Wallace, Lindsey Romick-Rosendale, Miki Watanabe-Chailland, David B. Haslam, Adam Lane, Stella M. Davies
Low levels of vitamin A have been associated with the development of gastrointestinal graft-versus-host disease (GVHD). Khandelwal et al report on the results of a randomized, placebo-controlled phase 2 trial in which a single dose of oral vitamin A given to children prior to conditioning resulted in no improvement in the incidence of acute GVHD compared to placebo but was associated with lower rates
-
Follow-up from the A041202 study shows continued efficacy of ibrutinib regimens for older adults with CLL Blood (IF 20.3) Pub Date : 2024-01-14 Jennifer A. Woyach, Gabriela Perez Burbano, Amy S. Ruppert, Cecelia Miller, Nyla A. Heerema, Weiqiang Zhao, Anna Wall, Wei Ding, Nancy L. Bartlett, Danielle M. Brander, Paul M. Barr, Kerry A. Rogers, Sameer A. Parikh, Deborah M. Stephens, Jennifer R. Brown, Gerard Lozanski, James Blachly, Sreenivasa Nattam, Richard A. Larson, Harry Erba, Mark Litzow, Selina Luger, Carolyn Owen, Charles Kuzma, Jeremy
A041202 (NCT01886872) is a phase 3 study comparing bendamustine plus rituximab (BR) with ibrutinib and the combination of ibrutinib plus rituximab (IR) in previously untreated older patients with chronic lymphocytic leukemia (CLL). The initial results showed that ibrutinib-containing regimens had superior progression-free survival (PFS) and rituximab did not add additional benefits. Here we present
-
Genetic mechanisms underlying tumor microenvironment composition and function in diffuse large B-cell lymphoma Blood (IF 20.3) Pub Date : 2024-01-13 Leandro Cerchietti
[Display omitted]
-
KBTBD4-mediated reduction of MYC is critical for hematopoietic stem cell expansion upon UM171 treatment Blood (IF 20.3) Pub Date : 2024-01-13 Jalila Chagraoui, Simon Girard, Laure Mallinger, Nadine Mayotte, Maria Florencia Tellechea, Guy Sauvageau
Ex vivo expansion of hematopoietic stem cells (HSCs) is gaining importance for cell and gene therapy, and requires a shift from dormancy state to activation and cycling. However, abnormal or excessive HSC activation results in reduced self-renewal ability and increased propensity for myeloid-biased differentiation. We now report that activation of the E3 ligase complex CRL3 by UM171 not only induces
-
First-hit SETBP1 mutations cause a myeloproliferative disorder with bone marrow fibrosis Blood (IF 20.3) Pub Date : 2024-01-11 Ilaria Crespiatico, Mattia Zaghi, Cristina Mastini, Deborah D’Aliberti, Mario Mauri, Carl Mirko Mercado, Diletta Fontana, Silvia Spinelli, Valentina Crippa, Elena Inzoli, Beatrice Manghisi, Ivan Civettini, Daniele Ramazzotti, Valentina Sangiorgio, Michele Gengotti, Virginia Brambilla, Andrea Aroldi, Federica Banfi, Cristiana Barone, Roberto Orsenigo, Ludovica Riera, Mara Riminucci, Alessandro Corsi
mutations are found in various clonal myeloid disorders. However, it is unclear whether they can initiate leukemia, because mutations typically appear as later events during oncogenesis. To answer this question, we generated a mouse model expressing mutated SETBP1 in hematopoietic tissue: this model showed profound alterations in the differentiation program of hematopoietic progenitors and developed
-
The follicular lymphoma tumor microenvironment at single-cell and spatial resolution Blood (IF 20.3) Pub Date : 2024-01-11 Andrea J. Radtke, Mark Roschewski
[Display omitted]
-
Lactate administration improves laboratory parameters in murine models of iron overload Blood (IF 20.3) Pub Date : 2024-01-11 Wei Liu, Yue Wu, Huaiqing Wei, Juan Ma, Wenya Feng, Qiuyuan Yang, Shuping Zhang, Tomas Ganz, Sijin Liu
Current iron overload therapeutics have inherent drawbacks including perpetuated low hepcidin. Here, we unveiled that lactate, a potent hepcidin agonist, effectively reduced serum and hepatic iron levels in mouse models of iron overload with an improved erythropoiesis in β-thalassemic mice.
-
Noncoding mutations drive persistence of a founder preleukemic clone which initiates late relapse in T-ALL Blood (IF 20.3) Pub Date : 2024-01-11 David O’Connor, Jose Espejo Valle-Inclán, Lucia Conde, Gianna Bloye, Sunniyat Rahman, Joana R. Costa, Jack Bartram, Stuart Adams, Gary Wright, Hillary Elrick, Kerry Wall, Sara Dyer, Christopher Howell, Galina Jigoulina, Javier Herrero, Isidro Cortes-Ciriano, Anthony V. Moorman, Marc R. Mansour
T-ALL relapse usually occurs early but can occur much later, which has been suggested to represent a de novo leukemia. However, we conclusively demonstrate late relapse can evolve from a pre-leukemic subclone harbouring a non-coding mutation that evades initial chemotherapy.
-
Arterio-occlusive events among patients with chronic myeloid leukemia on tyrosine kinase inhibitors Blood (IF 20.3) Pub Date : 2024-01-11 Lukas Veltmaat, Jorge Cortes
-
Developmental trajectories and cooperating genomic events define molecular subtypes of BCR::ABL1-positive ALL Blood (IF 20.3) Pub Date : 2023-12-30 Lorenz Bastian, Thomas Beder, Malwine J. Barz, Sonja Bendig, Lorenz Bartsch, Wencke Walter, Nadine Wolgast, Björn Brändl, Christian Rohrandt, Björn-Thore Hansen, Alina M. Hartmann, Katharina Iben, Dennis Das Gupta, Miriam Denker, Johannes Zimmermann, Michael Wittig, Guranda Chitadze, Martin Neumann, Folker Schneller, Walter Fiedler, Björn Steffen, Matthias Stelljes, Christoph Faul, Stefan Schwartz
Distinct diagnostic entities within ::positive acute lymphoblastic leukemia (ALL) are currently defined by the International Consensus Classification of myeloid neoplasms and acute leukemias (ICC): “lymphoid only”, with :: observed exclusively in lymphatic precursors, vs “multilineage”, where :: is also present in other hematopoietic lineages. Here, we analyzed transcriptomes of 327 ::positive patients
-
Targeting of the CD161 inhibitory receptor enhances T-cell–mediated immunity against hematological malignancies Blood (IF 20.3) Pub Date : 2023-12-30 Francesca Alvarez Calderon, Byong H. Kang, Oleksandr Kyrysyuk, Shiwei Zheng, Hao Wang, Nathan D. Mathewson, Adrienne M. Luoma, Xiaohan Ning, Jason Pyrdol, Xuan Cao, Mario L. Suvà, Guo-Cheng Yuan, K. Dane Wittrup, Kai W. Wucherpfennig
Alvarez Calderon and colleagues report on developing a fully human monoclonal antibody that disrupts the interaction between the inhibitory receptor CD161 on blood cancer cells and its ligand, CLEC2D. CD161 blockade enhances natural killer cell and T-cell effector function against malignant B cells, highlighting the potential for targeting CD161 as a novel future immunotherapeutic strategy in hematological
-
Whole-genome CRISPR screening identifies molecular mechanisms of PD-L1 expression in adult T-cell leukemia/lymphoma Blood (IF 20.3) Pub Date : 2023-12-27 Masahiro Chiba, Joji Shimono, Keito Suto, Takashi Ishio, Tomoyuki Endo, Hideki Goto, Hiroo Hasegawa, Michiyuki Maeda, Takanori Teshima, Yibin Yang, Masao Nakagawa
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive T-cell malignancy with a poor prognosis and limited treatment options. Programmed cell death ligand 1(PD-L1) is recognized to be involved in the pathobiology of ATLL. However, what molecules control PD-L1 expression and whether genetic or pharmacological intervention might modify PD-L1 expression in ATLL cells are still unknown. To comprehend the
-
Type 1 VWD classification revisited: novel insights from combined analysis of the LoVIC and WiN studies Blood (IF 20.3) Pub Date : 2023-12-27 Ferdows Atiq, Robin Blok, Calvin B. van Kwawegen, Dearbhla Doherty, Michelle Lavin, Johanna G. van der Bom, Niamh M. O'Connell, Joke de Meris, Kevin Ryan, Saskia E. M. Schols, Mary Byrne, Floor C. J. I. Heubel-Moenen, Karin P. M. van Galen, Roger J. S. Preston, Marjon H. Cnossen, Karin Fijnvandraat, Ross I. Baker, Karina Meijer, Paula James, Jorge Di Paola, Jeroen Eikenboom, Frank W. G. Leebeek, James
There is significant ongoing debate regarding type 1 von Willebrand disease (VWD) defintion. Previous guidelines recommended patients with von Willebrand factor (VWF) levels <30 IU/dL be diagnosed type 1 VWD, whereas patients with significant bleeding and VWF levels from 30 to 50 IU/dL be diagnosed with low VWF. To elucidate the relationship between type 1 VWD and low VWF in the context of age-induced
-
Targeting the tissue factor coagulation initiation complex prevents antiphospholipid antibody development Blood (IF 20.3) Pub Date : 2023-12-27 Nadine Müller-Calleja, Kristin Grunz, T. Son Nguyen, Jens Posma, Denise Pedrosa, Myriam Meineck, Anne Hollerbach, Johannes Braun, Sabine Muth, Hansjörg Schild, Kathrin Saar, Norbert Hübner, Sriram Krishnaswamy, Jennifer Royce, Luc Teyton, Niels Lemmermann, Julia Weinmann-Menke, Karl J. Lackner, Wolfram Ruf
Circulating antiphospholipid antibodies (aPLs) are an important risk factor for the development of thrombosis and pregnancy complications, and while we understand how they cause these clinical diseases, their etiology has been unknown. Müller-Calleja and colleagues reveal that tissue factor (TF) is vital for the development of autoantibodies against phospholipids in murine models. The authors show