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Reduction of mortality, cardiac damage, and cerebral damage by IL-1 inhibition in a murine model of TTP Blood (IF 20.3) Pub Date : 2024-04-10 Romain Muller, Raphaël Cauchois, Marie Lagarde, Sandrine Roffino, Cécile Genovesio, Samantha Fernandez, Guillaume Hache, Benjamin Guillet, Yéter Kara, Marion Marlinge, Peter Lenting, Pascale Poullin, Françoise Dignat-George, Edwige Tellier, Gilles Kaplanski
Thrombotic thrombocytopenic purpura (TTP), a rare but fatal disease if untreated, is due to alteration in von Willebrand factor cleavage resulting in capillary microthrombus formation and ischemic organ damage. Interleukin-1 (IL-1) has been shown to drive sterile inflammation after ischemia and could play an essential contribution to postischemic organ damage in TTP. Our objectives were to evaluate
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Mutational and transcriptional landscape of pediatric B-cell precursor lymphoblastic lymphoma Blood (IF 20.3) Pub Date : 2024-04-09 Emma Kroeze, Ingram Iaccarino, Michelle M. Kleisman, Mayukh Mondal, Thomas Beder, Mouhamad Khouja, Marc P Hoeppner, Marijn A. Scheijde-Vermeulen, Lennart A. Kester, Monika Brüggemann, Claudia D. Baldus, Gunnar Cario, Reno S. Bladergroen, Nathalie Garnier, Andishe Attarbaschi, Jaime Verdu-Amoros, Rosemary Sutton, Elizabeth MacIntyre, Kenneth Scholten, Laura Arias Padilla, Birgit Burkhardt, Auke Beishuizen
Pediatric B-cell precursor (BCP) lymphoblastic malignancies are neoplasms with manifestation either in the bone marrow or blood (BCP acute lymphoblastic leukemia [BCP-ALL]) or are less common in extramedullary tissue (BCP lymphoblastic lymphoma [BCP-LBL]). Although both presentations are similar in morphology and immunophenotype, molecular studies have been virtually restricted to BCP-ALL so far. The
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IL-18-secreting multiantigen targeting CAR T cells eliminate antigen-low myeloma in an immunocompetent mouse model Blood (IF 20.3) Pub Date : 2024-04-08 Brandon D. Ng, Adhithi Rajagopalan, Anastasia I. Kousa, Jacob S. Fischman, Sophia Chen, Alyssa Massa, Harold K. Elias, Dylan Manuele, Michael Galiano, Andri L. Lemarquis, Alexander P. Boardman, Susan DeWolf, Jonah Pierce, Bjarne Bogen, Scott E. James, Marcel R. M. van den Brink
Multiple myeloma is a plasma cell malignancy that is currently incurable with conventional therapies. Following the success of CD19-targeted chimeric antigen receptor (CAR) T cells in leukemia and lymphoma, CAR T cells targeting B-cell maturation antigen (BCMA) more recently demonstrated impressive activity in relapsed and refractory myeloma patients. However, BCMA-directed therapy can fail due to
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Loss of the stress sensor GADD45A promotes stem cell activity and ferroptosis resistance in LGR4/HOXA9-dependent AML Blood (IF 20.3) Pub Date : 2024-04-08 Nunki Hassan, Hangyu Yi, Bilal Malik, Lucie Gaspard-Boulinc, Saumya E. Samaraweera, Debora A. Casolari, Janith Seneviratne, Anushree Balachandran, Tracy Chew, Alastair Duly, Daniel R. Carter, Belamy B. Cheung, Murray Norris, Michelle Haber, Maria Kavallaris, Glenn M. Marshall, Xu Dong Zhang, Tao Liu, Jianlong Wang, Dan A. Liebermann, Richard J. D’Andrea, Jenny Y. Wang
The overall prognosis of acute myeloid leukemia (AML) remains dismal, largely because of the inability of current therapies to kill leukemia stem cells (LSCs) with intrinsic resistance. Loss of the stress sensor GADD45A is implicated in poor clinical outcomes, but its role in LSCs and AML pathogenesis is unknown. Here, we define GADD45A as a key downstream target of LGR4 oncogenic signaling and discover
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Bone marrow niches for hematopoietic stem cells: life span dynamics and adaptation to acute stress Blood (IF 20.3) Pub Date : 2024-04-08 Johanna Hofmann, Konstantinos D. Kokkaliaris
Hematopoietic stem cells (HSCs) are instrumental for organismal survival because 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
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A way to “mimic” the pathophysiology of acquired SAA Blood (IF 20.3) Pub Date : 2024-04-04 Amy E. DeZern
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Soft tick relapsing fever in a traveler returning from Colorado Blood (IF 20.3) Pub Date : 2024-04-04 Jill Schuett, Eduard Matkovic
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A treatment bridge for infants with hemophilia Blood (IF 20.3) Pub Date : 2024-04-04 Thomas C. Abshire
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Uncovering new layers of Ph+ ALL biology Blood (IF 20.3) Pub Date : 2024-04-04 Rathana Kim, Emmanuelle Clappier
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An evolving understanding of low VWF and type 1 VWD Blood (IF 20.3) Pub Date : 2024-04-04 Nathan T. Connell
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Axicabtagene ciloleucel vs standard of care in second-line large B-cell lymphoma: outcomes by metabolic tumor volume Blood (IF 20.3) Pub Date : 2024-04-03 Frederick L. Locke, Olalekan O. Oluwole, John Kuruvilla, Catherine Thieblemont, Franck Morschhauser, Gilles 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-[F]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 or less] vs high [greater than median]) and clinical outcomes in the phase 3 ZUMA-7 study (NCT03391466)
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B-cell–directed CAR T-cell therapy activates CD8+ cytotoxic CARneg bystander T cells in nonhuman primates and human patients Blood (IF 20.3) Pub Date : 2024-04-03 James Kaminski, Ryan A. Fleming, Francesca Alvarez-Calderon, Marlana B. Winschel, Connor McGuckin, Emily E. Ho, Fay Eng, Xianliang Rui, Paula Keskula, Lorenzo Cagnin, Joanne Charles, Jillian Zavistaski, Steven P. Margossian, Malika A. Kapadia, James B. Rottman, Jennifer Lane, Susanne H. C. Baumeister, Victor Tkachev, Alex K. Shalek, Leslie S. Kean, Ulrike Gerdemann
Chimeric antigen receptor (CAR) T cells hold promise as a therapy for B-cell–derived malignancies, and despite their impressive initial response rates, a significant proportion of patients ultimately experience relapse. Although recent studies have explored the mechanisms of in vivo CAR T-cell function, little is understood about the activation of surrounding CAR bystander T cells and their potential
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Loss of GABARAP mediates resistance to immunogenic chemotherapy in multiple myeloma Blood (IF 20.3) Pub Date : 2024-04-02 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 Prabhala, Giada Bianchi, Mariateresa Fulciniti, Kenneth Wen, Keiji Kurata, Jiye Liu, Johany Penailillo, Alberto Bragoni, Anna Sapino, Paul G. Richardson, Dharminder
Immunogenic cell death (ICD) is a form of cell death by which cancer treatments can induce a clinically relevant antitumor 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
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Younger unrelated donors may be preferable over HLA match in the PTCy era: a study from the ALWP of the EBMT Blood (IF 20.3) Pub Date : 2024-04-01 Jaime Sanz, Myriam Labopin, Goda Choi, Alexander Kulagin, Jacopo Peccatori, Jan Vydra, Péter Reményi, Jurjen Versluis, Montserrat Rovira, Didier Blaise, Hélène Labussière-Wallet, Juan Montoro, Simona Sica, Ellen Meijer, Maija Itäla-Remes, Nicolaas Schaap, Claude Eric Bulabois, Simona Piemontese, Mohamad Mohty, Fabio Ciceri
There is a paucity of information on how to select the most appropriate unrelated donor (UD) in hematopoietic stem cell transplantation (HSCT) using posttransplant cyclophosphamide (PTCy). We retrospectively analyzed the characteristics of 10/10 matched UDs (MUDs) and 9/10 mismatched UDs (MMUDs) that may affect transplant outcomes in patients with acute myeloid leukemia (AML) in first or second complete
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Genomic determinants of response and resistance to inotuzumab ozogamicin in B-cell ALL Blood (IF 20.3) Pub Date : 2024-04-01 Yaqi Zhao, Nicholas J. Short, Hagop M. Kantarjian, Ti-Cheng Chang, Pankaj S. Ghate, Chunxu Qu, Walid Macaron, Nitin Jain, Beenu Thakral, Aaron H. Phillips, Joseph Khoury, Guillermo Garcia-Manero, Wenchao Zhang, Yiping Fan, Hui Yang, Rebecca S. Garris, Lewis F. Nasr, Richard W. Kriwacki, Kathryn G. Roberts, Marina 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 the response and resistance to InO. Pre- and post-InO–treated patient samples were analyzed by whole-genome, exome, and/or transcriptome sequencing
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Unraveling MCL biology to understand resistance and identify vulnerabilities Blood (IF 20.3) Pub Date : 2024-04-01 Clémentine Sarkozy, Benoit Tessoulin, David Chiron
Mantle cell lymphoma (MCL) is a rare (5%-7%), aggressive B-cell non-Hodgkin lymphoma with well-defined hallmarks (eg, cyclin D1, SOX11), and its expansion is highly dependent on the tumor microenvironment (TME). Parallel drastic progress in the understanding of lymphomagenesis and improved treatments led to a paradigm shift in this B-cell malignancy with now prolonged disease-free survival after intensive
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Excess of circulating apotransferrin enhances dietary iron absorption in mice Blood (IF 20.3) Pub Date : 2024-03-27 Sofiya Tsyplenkova, Edouard Charlebois, Carine Fillebeen, Kostas Pantopoulos
Intravenous injection of excess apotransferrin enhances dietary iron absorption in mice and triggers accumulation of plasma non–transferrin-bound iron. Injected fluorescent-labeled transferrin colocalizes with lamina propria macrophages, consistent with the recently proposed iron absorption checkpoint involving macrophage-mediated transferrin degradation.
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Genetic regulation of carnitine metabolism controls lipid damage repair and aging RBC hemolysis in vivo and in vitro Blood (IF 20.3) Pub Date : 2024-03-26 Travis Nemkov, Alicia Key, Daniel Stephenson, Eric J. Earley, Gregory R. Keele, Ariel Hay, Pascal Amireault, Madeleine Casimir, Michaël Dussiot, Monika Dzieciatkowska, Julie A. Reisz, Xutao Deng, Mars Stone, Steve Kleinman, Steven L. Spitalnik, Kirk C. Hansen, Philip J. Norris, Gary A. Churchill, Michael P. Busch, Nareg Roubinian, Grier P. Page, James C. Zimring, Arduino Arduini, Angelo D’Alessandro
Recent large-scale multiomics 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 2 separate occasions. These analyses identified carnitine metabolism as the most reproducible pathway across multiple donations from
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Landscape of driver mutations and their clinical effects on down syndrome–related myeloid neoplasms Blood (IF 20.3) Pub Date : 2024-03-26 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
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
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Paroxysmal nocturnal hemoglobinuria–related thrombosis in the era of novel therapies: a 2043–patient-year analysis Blood (IF 20.3) Pub Date : 2024-03-26 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 1 of the principal features of paroxysmal nocturnal hemoglobinuria (PNH) and constitutes the main cause of disease morbidity/mortality. Anticomplement treatment has revolutionized the natural history of PNH, with control of the hemolytic process and abolition of thrombotic events (TEs). However, no guidelines exist for the management of thromboembolic complications in this setting
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Genomic imbalance analysis provides new insight into prognostic factors in adult and pediatric T-ALL Blood (IF 20.3) Pub Date : 2024-03-25 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 Andrieu, Aurore Touzart, Françoise Huguet, Arnaud Petit, Norbert Ifrah, Hervé Dombret, André Baruchel, Elizabeth Macintyre, Claude Preudhomme, Nicolas Boissel, Vahid Asnafi
Given the poor outcome of refractory and relapsing T-cell acute lymphoblastic leukemia (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 patients with T-ALL including 135 children and 182 adults with respect to clinical and biological features and outcomes. SNP array results
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The IL-7R antagonist lusvertikimab reduces leukemic burden in xenograft ALL via antibody-dependent cellular phagocytosis Blood (IF 20.3) Pub Date : 2024-03-25 Lennart Lenk, Irène Baccelli, Anna Laqua, Julia Heymann, Claas Reimer, Anna Dietterle, Dorothee Winterberg, Caroline Mary, Frédérique Corallo, Julien Taurelle, Emma Narbeburu, Stéphanie 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
Acute lymphoblastic leukemia (ALL) arises from the uncontrolled proliferation of B-cell precursor (BCP)- or T-cell ALL (BCP-ALL 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 (HR) leukemias and T-ALL, in which immunotherapy approaches remain
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An oral carbon monoxide–releasing molecule protects against acute hyperhemolysis in sickle cell disease Blood (IF 20.3) Pub Date : 2024-03-25 Kim-Anh Nguyen, Alessandro Matte, Roberta Foresti, Enrica Federti, Laurent Kiger, Cécile Lefebvre, Hakim Hocini, Yanis Pelinski, Hiroaki Kitagishi, Laura Bencheikh, France Pirenne, Lucia de Franceschi, Roberto Motterlini, Pablo Bartolucci
Acute hyperhemolysis 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 multiorgan failure. Here, we developed in vitro and in vivo animal models to mimic endothelial damage during the early phase of hyperhemolysis in SCD. We then used the carbon monoxide (CO)-releasing
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Heparan sulfates and heparan sulfate proteoglycans in hematopoiesis Blood (IF 20.3) Pub Date : 2024-03-25 Richard T. Piszczatowski, Hannes E. Bülow, Ulrich Steidl
From signaling mediators in stem cells to markers of differentiation and lineage commitment to facilitators for the entry of viruses, such as HIV-1, cell surface heparan sulfate (HS) glycans with distinct modification patterns play important roles in hematopoietic biology. In this review, we provide an overview of the importance of HS and the proteoglycans (HSPGs) to which they are attached within
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Endothelial ZIP8 plays a minor role in BMP6 regulation by iron in mice Blood (IF 20.3) Pub Date : 2024-03-25 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 bone morphogenetic protein (BMP6) expression by liver endothelial cells is essential for iron homeostasis regulation. We used multiple dietary and genetic mouse cohorts to demonstrate a minor functional role for ZRT/IRT-like protein 8 in regulating BMP6 expression under high-iron conditions.
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Peak ADAMTS13 activity to assess ADAMTS13 conformation and risk of relapse in immune-mediated thrombotic thrombocytopenic purpura Blood (IF 20.3) Pub Date : 2024-03-21 Nithya Prasannan, Bertina Dragunaite, Maryam Subhan, Mari Thomas, Rens de Groot, Deepak Singh, Karen Vanhoorelbeke, Marie Scully
Previous studies have demonstrated that >38% of patients with immune-mediated thrombotic thrombocytopenic purpura in remission with activity >50% had an open ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13) conformation. We assessed ADAMTS13 conformation in remission (ADAMTS13 activity >60%), focusing on peak ADAMTS13 activity levels and longitudinal assessment
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Malignant progression of preleukemic disorders Blood (IF 20.3) Pub Date : 2024-03-20 Trent Hall, Sandeep Gurbuxani, John D. Crispino
The spectrum of myeloid disorders ranges from aplastic bone marrow failure characterized by an empty bone marrow completely lacking in hematopoiesis to acute myeloid leukemia in which the marrow space is replaced by undifferentiated leukemic blasts. Recent advances in the capacity to sequence bulk tumor population as well as at a single-cell level has provided significant insight into the stepwise
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Frontline management of mantle cell lymphoma Blood (IF 20.3) Pub Date : 2024-03-20 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
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A lineage-specific STAT5BN642H mouse model to study NK-cell leukemia Blood (IF 20.3) Pub Date : 2024-03-20 Klara Klein, Sebastian Kollmann, Angela Hiesinger, Julia List, Jonatan Kendler, Thorsten Klampfl, Mehak Rhandawa, Jana Trifinopoulos, Barbara Maurer, Reinhard Grausenburger, Christof A. Betram, Richard Moriggl, Thomas Rülicke, Charles G. Mullighan, Agnieszka Witalisz-Siepracka, Wencke Walter, Gregor Hoermann, Veronika Sexl, Dagmar Gotthardt
Patients with T- and natural killer (NK)-cell neoplasms frequently have somatic gain-of-function mutations. The most frequent mutation is , which is known to drive murine T-cell leukemia, although its role in NK-cell malignancies is unclear. Introduction of the mutation into human NK-cell lines enhances their potential to induce leukemia in mice. We have generated a mouse model that enables tissue-specific
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The TLK-ASF1 histone chaperone pathway plays a critical role in IL-1β–mediated AML progression Blood (IF 20.3) Pub Date : 2024-03-20 Hsin-Yun Lin, Mona Mohammadhosseini, John McClatchy, Marina Villamor-Payà, Sophia Jeng, Daniel Bottomly, Chia-Feng Tsai, Camilo Posso, Jeremy Jacobson, Andrew Adey, Sara Gosline, Tao Liu, Shannon McWeeney, Travis H. Stracker, Anupriya Agarwal
Identifying and targeting microenvironment-driven pathways that are active across acute myeloid leukemia (AML) genetic subtypes should allow the development of more broadly effective therapies. The proinflammatory cytokine interleukin-1β (IL-1β) is abundant in the AML microenvironment and promotes leukemic growth. Through RNA-sequencing analysis, we identify that IL-1β–upregulated ASF1B (antisilencing
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Thrombosis risk in single- and double-heterozygous carriers of factor V Leiden and prothrombin G20210A in FinnGen and the UK Biobank Blood (IF 20.3) Pub Date : 2024-03-20 Justine Ryu, Joel T. Rämö, Sean J. Jurgens, FinnGen, 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 2 of the most well-studied genetic risk factors for venous thromboembolism (VTE). However, double heterozygosity (DH) for FVL and PTGM remains poorly understood, with previous studies showing marked disagreement regarding thrombosis risk conferred by the DH genotype. Using multidimensional data from the UK
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Evidence for antigen presentation by human neutrophils Blood (IF 20.3) Pub Date : 2024-03-20 Angus Moffat, Emily Gwyer Findlay
Neutrophils are the first migrating responders to sterile and infectious inflammation and act in a powerful but nonspecific fashion to kill a wide variety of pathogens. It is now apparent 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
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Integration of ζ-deficient CARs into the CD3-zeta gene conveys potent cytotoxicity in T and NK cells Blood (IF 20.3) Pub Date : 2024-03-19 Jonas Kath, Clemens Franke, Vanessa Drosdek, Weijie Du, Viktor Glaser, Carla Fuster-Garcia, Maik Stein, Tatiana Zittel, Sarah Schulenberg, Caroline E. Porter, Lena Andersch, Annette Künkele, Joshua Alcaniz, Jens Hoffmann, Hinrich Abken, Mohamed Abou-el-Enein, Axel Pruß, Masataka Suzuki, Toni Cathomen, Renata Stripecke, Hans-Dieter Volk, Petra Reinke, Michael Schmueck-Henneresse, Dimitrios L. Wagner
Chimeric antigen receptor (CAR)-redirected immune cells hold significant therapeutic potential for oncology, autoimmune diseases, transplant medicine, and infections. All approved CAR-T therapies rely on personalized manufacturing using undirected viral gene transfer, which results in non-physiological regulation of CAR-signaling and limits their accessibility due to logistical challenges, high costs
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Mutations causing premature termination codons discriminate and generate cellular and clinical variability in HHT Blood (IF 20.3) Pub Date : 2024-03-19 Maria E. Bernabeu-Herrero, Dilip Patel, Adrianna Bielowka, JiaYi Zhu, Kinshuk Jain, Ian S. Mackay, Patricia Chaves Guerrero, Giulia Emanuelli, Luca Jovine, Michela Noseda, Stefan J. Marciniak, Micheala A. Aldred, Claire L. Shovlin
For monogenic diseases caused by pathogenic loss-of-function DNA variants, attention focuses on dysregulated gene-specific pathways, usually considering molecular subtypes together within causal genes. To better understand phenotypic variability in hereditary hemorrhagic telangiectasia (HHT), we subcategorized pathogenic DNA variants in /endoglin, /ALK1, and if they generated premature termination
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Loss of Dnmt3a increases self-renewal and resistance to pegIFN-α in JAK2-V617F–positive myeloproliferative neoplasms Blood (IF 20.3) Pub Date : 2024-03-18 Marc Usart, Jan Stetka, Damien Luque Paz, Nils Hansen, Quentin Kimmerlin, Tiago Almeida Fonseca, Melissa Lock, Lucia Kubovcakova, Riikka Karjalainen, Hui Hao-Shen, Anastasiya Börsch, Athimed El Taher, Jessica Schulz, Jean-Christophe Leroux, Stefan Dirnhofer, Radek C. Skoda
Pegylated interferon alfa (pegIFN-α) can induce molecular remissions in patients with -V617F–positive myeloproliferative neoplasms (MPNs) by targeting long-term hematopoietic stem cells (LT-HSCs). Additional somatic mutations in genes regulating LT-HSC self-renewal, such as , have been reported to have poorer responses to pegIFN-α. We investigated whether loss leads to alterations in -V617F LT-HSC
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Management of adult patients with CMML undergoing allo-HCT: recommendations from the EBMT PH&G Committee Blood (IF 20.3) Pub Date : 2024-03-18 Francesco Onida, Nico Gagelmann, Yves Chalandon, Guido Kobbe, Marie Robin, Argiris Symeonidis, Theo de Witte, Raphael Itzykson, Madlen Jentzsch, Uwe Platzbecker, Valeria Santini, Guillermo Sanz, Christof Scheid, Eric Solary, Peter Valent, Raffaela Greco, Isabel Sanchez-Ortega, Ibrahim Yakoub-Agha, Lisa Pleyer
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An international learning collaborative phase 2 trial for haploidentical bone marrow transplant in sickle cell disease Blood (IF 20.3) Pub Date : 2024-03-18 Adetola A. Kassim, Josu de la Fuente, Erfan Nur, Karina L. Wilkerson, Ali D. Alahmari, Adriana Seber, Carmem Bonfim, Belinda Pinto Simões, Mohsen Alzahrani, Michael J. Eckrich, Biljana Horn, Rabi Hanna, Nathalie Dhedin, Hemalatha G. Rangarajan, Roseane Vasconcelos Gouveia, Fahad Almohareb, Mahmoud Aljurf, Mohammed Essa, Bader Alahmari, Katie Gatwood, James A. Connelly, Elisabeth Dovern, Mark Rodeghier
In the setting of a learning collaborative, we conducted an international multicenter phase 2 clinical trial testing the hypothesis that nonmyeloablative–related haploidentical bone marrow transplant (BMT) with thiotepa and posttransplant cyclophosphamide (PTCy) will result in 2-year event-free survival (no graft failure or death) of at least 80%. A total of 70 participants were evaluable based on
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Glofitamab stimulates immune cell infiltration of CNS tumors and induces clinical responses in secondary CNS lymphoma Blood (IF 20.3) Pub Date : 2024-03-17 James K. Godfrey, Lei Gao, Geoffrey Shouse, Joo Y. Song, Stacy Pak, Brian Lee, Bihong T. Chen, Avyakta Kallam, John H. Baird, Guido Marcucci, Lucy Ghoda, Stephanie Vauleon, Alexey V. Danilov, Alex F. Herrera, Larry W. Kwak, Lihua E. Budde
Although CD20×CD3 bispecific antibodies are effective against systemic B-cell lymphomas, their efficacy in central nervous system (CNS) lymphoma is unknown. Here, we report the CD20×CD3 bispecific, glofitamab, penetrates the blood-brain barrier, stimulates immune-cell infiltration of CNS tumors, and induces clinical responses in secondary CNS lymphoma patients.
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Second primary malignancies after commercial CAR T-cell therapy: analysis of FDA Adverse Events Reporting System Blood (IF 20.3) Pub Date : 2024-03-15 Magdi Elsallab, Moataz Ellithi, Matthew A. Lunning, Christopher D’Angelo, Jihyun Ma, Miguel-Angel Perales, Matthew Frigault, Marcela V. Maus
Second primary malignancies were reported in 536 of 12 394 (4.3%) adverse event reports following chimeric antigen receptor T-cell therapies in the Food and Drug Administration Adverse Event Reporting System. Myeloid and T-cell neoplasms were disproportionately more frequently reported, warranting further follow-up.
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Systemic mastocytosis: dying or survivin Blood (IF 20.3) Pub Date : 2024-03-14 Joakim S. Dahlin, Gunnar Nilsson
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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
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Hemolysis impairs sickle cell erythropoiesis Blood (IF 20.3) Pub Date : 2024-03-14 Constance T. Noguchi
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Monomorphic epitheliotropic T-cell lymphoma with strong CD4 expression Blood (IF 20.3) Pub Date : 2024-03-14 Siba El Hussein
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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 Jaju, Allison Lam, Yoav H. Messinger, Rodney R. Miles, Maki Okada, Samir Patel, Eric S. Schafer, Tal Schechter, Kristin A. Shimano
Defining prognostic variables in T-lymphoblastic lymphoma (T-LL) remains a challenge. AALL1231 was a Children’s Oncology Group phase 3 clinical trial for newly diagnosed patients with T acute lymphoblastic leukemia or T-LL, randomizing children and young adults to a modified augmented Berlin-Frankfurt-Münster backbone to receive standard therapy (arm A) or with addition of bortezomib (arm B). Optional
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In vivo ablation of NF-κB 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 NF-κB cascade propagates oncogenic signaling and proinflammation, which together augments disease burden in myeloproliferative neoplasms (MPNs). Here, we systematically ablate NF-κB 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
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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. Germ line 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
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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 (cyclophosphamide-vincristine-adriamycin-dexamethasone) cycle 1 when combined with imatinib in adults with Philadelphia-positive acute lymphoblastic leukemia. In the present randomized GRAAPH-2014 trial, we used nilotinib and addressed the omission of cytarabine (Ara-C) in consolidation. The primary
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Epigenetic control over the 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 Hennig, 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
Epigenetic modulation of the cell-intrinsic immune response holds promise as a therapeutic approach for leukemia. However, current strategies designed for transcriptional activation of endogenous transposons and subsequent interferon type-I (IFN-I) response, show limited clinical efficacy. Histone lysine methylation is an epigenetic signature in IFN-I response associated with suppression of IFN-I and
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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 natural killer (NK) cells. Prior in vitro studies in our laboratory demonstrated that T cells contribute to maintaining the viability and cytotoxic
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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 proinflammatory microenvironment suggests causative association between mutations and seronegative RA. Our findings merit investigation of inhibitors as therapeutics for seronegative -mutated RA.
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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 (Hb) 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 nonfunctional Hb Bart’s (γ) or HbH (β) resulting in severe anemia, tissue hypoxia, and, in some cases, variable congenital or neurocognitive abnormalities. BHFS is the most
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Fitusiran prophylaxis in people with hemophilia A or B who switched from prior BPA/CFC prophylaxis: the ATLAS-PPX trial 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 investigational small interfering RNA 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 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 (BPA)/clotting
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Vector integration and fate in the hemophilia dog liver multiple years after 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 virus (AAV) vectors is a promising approach for the treatment of monogenic disorders. Long-term multiyear 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
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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, 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
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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
Long noncoding RNAs (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