HemaSphere最新文献

{"title":"Mutant calreticulin-Cancer driver and Achilles' heel for ET?","authors":"Moritz Reichert, Bethan Psaila","doi":"10.1002/hem3.70368","DOIUrl":"https://doi.org/10.1002/hem3.70368","url":null,"abstract":"","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 4","pages":"e70368"},"PeriodicalIF":14.6,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13103721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional, biochemical, and clinical characterization of natural mutations affecting arginine residues in the heparin-binding site of antithrombin.","authors":"Rosa Cifuentes-Riquelme, María Eugenia de la Morena-Barrio, Antonia Miñano, Pedro Garrido-Rodríguez, Francisco Velasco, Juan José Rojo-Carrillo, Paloma López-Correas, David Zaragoza-Huesca, José Padilla, María Luisa Lozano, Carlos Bravo-Pérez, Javier Corral","doi":"10.1002/hem3.70338","DOIUrl":"https://doi.org/10.1002/hem3.70338","url":null,"abstract":"<p><p>Arginine residues in antithrombin are essential for heparin binding and for the activation of this key anticoagulant serpin. Mutations affecting these residues may cause antithrombin deficiency, specifically Type II heparin-binding site (HBS) defects, and increase the risk of thrombosis. However, previous alanine-scanning mutagenesis and crystallographic studies have yielded conflicting results regarding the specific residues involved in heparin binding. Our aim was to characterize natural variants affecting arginine residues in antithrombin. Genetic, biochemical, and functional characterization of antithrombin was done in 663 unrelated patients, most with antithrombin deficiency. Recombinant expression of the variants was performed in two different N-glycosylation backgrounds. We identified nine <i>SERPINC1</i> missense variants affecting eight arginine residues located at or near the HBS, four of them novel. Two variants, the most distant from the HBS (p.R291H and p.R177C), were found to be benign. In contrast, p.R45W, p.R56C, p.R79C, p.R79H, and p.R161Q caused Type II HBS deficiency. p.R78Q, causing a mild Type II HBS defect, was identified in a patient with compound heterozygosity with other HBS mutations. N-glycosylation at N167 modulated heparin affinity and influenced the clinical severity of mutations affecting arginine residues involved in heparin interaction. Finally, p.R89S caused Type I deficiency by creating a novel N-glycosylation motif, leading to hyperglycosylation and intracellular retention. Natural variants provide valuable insights into the functional contribution of arginine residues to antithrombin-heparin interaction. Our findings highlight the biochemical, functional, and clinical heterogeneity of these mutations and underscore the importance of comprehensive characterization for accurate diagnosis and prognosis in affected individuals.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 4","pages":"e70338"},"PeriodicalIF":14.6,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13100974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147770020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integration of circulating tumor DNA profiling in the risk stratification of classical Hodgkin lymphoma in children, adolescents, and young adults.","authors":"Mathieu Simonin, Mathieu Viennot, Stéphanie Haouy, Stéphane Ducassou, Catherine Curtillet, Nathalie Garnier, Aurélie Phulpin, Catherine Paillard, Charlotte Rigaud, Marie-Laure Couec, Liana Carausu, Jacinthe Bonneau, Isabelle Pellier, Melissa Barbati, Frédéric Millot, Marie-Émilie Dourthe, Justina Kanold, Pascale Schneider, Jean-Louis Stephan, Camille Leglise, Claire Pluchart, Pierre-Julien Viailly, Victor Michel, Sabah Boudjemaa, Bénédicte Jonca, Thierry Leblanc, Judith Landman-Parker, Fabrice Jardin","doi":"10.1002/hem3.70357","DOIUrl":"https://doi.org/10.1002/hem3.70357","url":null,"abstract":"<p><p>This study aimed to define the potential role of circulating tumor DNA (ctDNA) in children, adolescents, and young adults (CAYA) with classical Hodgkin lymphoma (cHL). This prospective trial was conducted in France between 2019 and 2023 and recruited CAYA patients (≤25 years old) with a new diagnosis of cHL. Patients were treated according to the EuroNet-PHL-C2 trial (EudraCT: 2012-004053-88), and plasma ctDNA evaluations were performed at diagnosis, after two cycles of chemotherapy, and in case of relapse. Two hundred and seventy-five patients were included. Median age at diagnosis was 15 years (range 2-22), and 47% of the patients were treated as advanced stages (treatment level 3 [TL-3]). Using an 18-gene amplicon-based next-generation sequencing (NGS) targeted panel encompassing the most frequently mutated genes in cHL, at least one mutation was detected in 236/275 patients (86%). B-symptoms, erythrocyte sedimentation rate, and advanced stages were significantly associated with the level of ctDNA at diagnosis. <i>TP53</i> mutations (19/275, 7%) were strongly associated with inadequate response at early response assessment. <i>XPO1 and IGLL5</i> mutations were associated with a higher risk of relapse. The presence of detectable ctDNA after two cycles of chemotherapy (10%) was a strong and independent prognostic marker of relapse.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 4","pages":"e70357"},"PeriodicalIF":14.6,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13093264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biological and clinical characteristics of <i>ETV6</i>::<i>RUNX1</i>-like ALL.","authors":"Marketa Zaliova, Dagmar Schinnerl, Judith M Boer, Aurélie Caye-Eude, Jacqueline Rehn, Claire Schwab, Chloé Arfeuille, Andishe Attarbaschi, Anke Katharina Bergmann, Karel Fiser, Hester A de Groot-Kruseman, Sabrina Haslinger, Andrea Inthal, Iveta Janotova, Lennart Lenk, Margarita Maurer-Granofszky, Karin Nebral, Fiona Poyer, Lucie Sramkova, Jan Stary, Marion Strullu, Jan Stuchly, Rosemary Sutton, Martina Vaskova, Lucie Winkowska, Gunnar Cario, Hélène Cavé, Monique L den Boer, Christine Harrison, Sabine Strehl, Deborah White, Jan Trka, Jan Zuna","doi":"10.1002/hem3.70342","DOIUrl":"10.1002/hem3.70342","url":null,"abstract":"<p><p><i>ETV6::RUNX1</i>-like ALL is defined by a gene expression signature similar to that of <i>ETV6::RUNX1</i>-positive ALL and absence of all genetic subtype-defining aberrations, including the <i>ETV6::RUNX1</i> fusion. Within the International BFM Study Group, we assembled and analyzed a cohort of 100 patients (including 97 children) with <i>ETV6::RUNX1</i>-like ALL. We describe their diverse genetic landscape, centered around <i>ETV6</i> aberrations with frequent <i>IKZF1</i> disruptions, as previously shown, but including various rare non-<i>ETV6</i>/non-<i>IKZF1</i> gene fusions, and rearrangements of <i>CRLF2</i> (<i>CRLF2</i>r). We show that <i>ETV6</i> and <i>IKZF1</i> aberrations do not occur exclusively in this subtype, which hampers its classification based solely on genomic data. We confirm our previous observation of a strong association of the CD27-positive/CD44low-negative immunophenotype with <i>ETV6</i>::<i>RUNX1</i>(-like) subtype. Compared to <i>ETV6::RUNX1</i>-positive ALL, patients with <i>ETV6::RUNX1</i>-like ALL are younger, have higher white blood cell counts at diagnosis, and have an inferior early treatment response. While overall survival is comparable, event-free survival is significantly lower in patients with <i>ETV6::RUNX1</i>-like ALL, with NCI risk, early treatment response, <i>IKZF1</i> deletions, <i>CRLF2r,</i> and <i>JAK2</i> mutations having prognostic relevance. Notably, Down syndrome is highly prevalent and associated with a worse outcome in <i>ETV6::RUNX1</i>-like ALL. In conclusion, we provide biological, demographic, and clinical characteristics of the largest <i>ETV6::RUNX1</i>-like cohort presented to date.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 4","pages":"e70342"},"PeriodicalIF":14.6,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13088304/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamics of complete responses (CRs) in patients with relapsed or refractory follicular lymphoma (R/R FL) treated with odronextamab in the ELM-2 study.","authors":"Stefano Luminari, Ana Jiménez-Ubieto, Geoffrey Chong, David Tucker, Srikanth Ambati, Chinjune Lin, Hesham Mohamed, Jurriaan Brouwer-Visser, Chetachi Akunna Otele, Giovanni Antico, Jose C Villasboas","doi":"10.1002/hem3.70300","DOIUrl":"https://doi.org/10.1002/hem3.70300","url":null,"abstract":"<p><p>Complete response (CR) is an important treatment goal in follicular lymphoma (FL). In relapsed or refractory (R/R) FL, CR rates decline, and disease progression accelerates with each treatment line, with particularly poor outcomes in patients with high-risk features. Odronextamab, a CD20 × CD3 bispecific antibody, demonstrated deep, durable responses and generally manageable safety in R/R FL in the Phase 2 ELM-2 study (NCT03888105); we present an exploratory analysis in patients who attained a CR. Patients received intravenous odronextamab with step-up dosing in Cycle 1, 80 mg weekly in Cycles 2-4, then 160 mg once every 2 weeks until disease progression or other protocol-defined reason for discontinuation. Patients with CR lasting ≥9 months switched to dosing once every 4 weeks. Overall, 73.4% (94/128) of patients attained CR, 93.6% (88/94) by first response assessment (~Week 12). Median time to CR was 2.7 months (range 2.3-7.9). Median duration of CR was 25.1 months (95% confidence interval [CI] 20.5-not evaluable [NE]) overall and 23.7 months (18.2-NE) in patients with high-risk features. Overall, 79.5% (35/44) of patients who switched to Q4W dosing maintained CR at last assessment. Patients with low/undetectable CD20 expression by immunohistochemistry (<10% CD20⁺ cells) or RNA sequencing (messenger RNA < 500 transcripts per million) could achieve CR. Median progression-free survival was 27.8 months (95% CI 23.0-NE) in patients with CR and not reached in those with undetectable circulating tumor DNA at Week 12. Treatment-emergent adverse events (TEAEs) led to treatment discontinuation in 16.0% of patients with CR; the most common TEAE was cytokine release syndrome (56.4%). This generally manageable safety profile and the sustainability of CRs support odronextamab as a potential long-term treatment for heavily pretreated R/R FL.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 4","pages":"e70300"},"PeriodicalIF":14.6,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13086623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematology in times of crisis: Lessons learned and strategic priorities from the EHA-ASH Joint Workshop on Ukraine.","authors":"Oleksandr Istomin, Taisiya Yakimkova, Reggie Belkhedim, Natacha Bolaños, Konstanze Döhner, Arnold Ganser, Torsten Haferlach, André Ilbawi, Arman Kacharian, Roman Kizyma, Sergiy Klymenko, Sybiryna Korenkova, Frank Leebeek, Oleksandr Lysytsia, Bohdan Medvediev, Wojciech Mlynarski, Dietger Niederwieser, Yuliya Nogovitsyna, Damiano Rondelli, Iryna Selina, Ganna Usenko, Nazar Shokun, Mats Heyman, Charlotte Niemeyer, Alexandra Müller","doi":"10.1002/hem3.70369","DOIUrl":"10.1002/hem3.70369","url":null,"abstract":"","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 4","pages":"e70369"},"PeriodicalIF":14.6,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084696/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IntegrateALL: An end-to-end RNA-seq analysis pipeline for multilevel data extraction and interpretable subtype classification in B-precursor ALL.","authors":"Nadine Wolgast, Thomas Beder, Mayukh Mondal, Wencke Walter, Stephan Hutter, Sonja Bendig, Jan Kässens, Björn-Thore Hansen, Katharina Iben, Sebastian Wolf, Anjali Cremer, Malwine Barz, Martin Neumann, Nicola Gökbuget, Claudia Haferlach, Monika Brüggemann, Claudia D Baldus, Alina M Hartmann, Lorenz Bastian","doi":"10.1002/hem3.70366","DOIUrl":"10.1002/hem3.70366","url":null,"abstract":"<p><p>Transcriptome sequencing (RNA-seq) is emerging as a diagnostic standard for B-cell precursor acute lymphoblastic leukemia (B-ALL). Expression-based classifiers reach ~95% accuracy, but reproducible end-to-end solutions that also integrate transcript-derived genomic drivers and quantitative virtual karyotyping are lacking. We developed IntegrateALL, a Snakemake pipeline that standardizes RNA-seq analysis from FASTQ to rule-based subtype assignment across 26 WHO-HAEM5/ICC entities by integrating expression-based subtype prediction, gene fusion-/hotspot SNV calling, and virtual karyotyping. We introduce KaryALL, a machine learning classifier that uses normalized expression and minor-allele-frequency features (RNASeqCNV), to distinguish near-haploid, hypodiploid, and high-hyperdiploid B-ALL and chromosome-21 gains/iAMP21 (accuracy: 0.98/F1 score: 0.96 on 615 independent test samples). SNP-array concordance supported RNA-based karyotyping. Applied to 774 unselected B-ALL cases, IntegrateALL yielded unambiguous subtype assignments in 81.5%, based on concordance of gene expression class with a defining driver (75.3% of all cases) or, in selected cases, high-confidence expression-based classification alone (6.2%); the remainder (18.5%) were flagged for manual curation. Independent validation (three cohorts; <i>n</i> = 436, including pediatric cases) reproduced these distributions. Across all patients (<i>n</i> = 1210), 2.6% harbored two subtype-defining drivers, including hyperdiploidy in fusion-driven subtypes, where it was not expected, or subtype-defining SNVs (e.g., <i>PAX5</i> P80R/<i>IKZF1</i> N159Y) co-occurring with <i>BCR::ABL1</i>-positive/-like, <i>KMT2A</i>-, or <i>DUX4</i>-fusions. In most dual-driver cases, one subtype gene expression signature predominated, consistent with oncogenic hierarchies, but also with the possibility of technical artifacts, which should prompt individual orthogonal validations. IntegrateALL provides an adaptable fully reproducible workflow for molecular B-ALL characterization by systematically integrating genomic drivers and downstream gene regulation.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 4","pages":"e70366"},"PeriodicalIF":14.6,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084704/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preclinical models of hepatosplenic γδ T-cell lymphoma with an activating STAT5B mutation display sensitivity to JAK inhibitor upadacitinib.","authors":"Myint Myat Khine Aung, Susann Schönefeldt, Sophie Pfalz-Kraupp, Tamara Wais, Tobias Suske, Safia Zahma, Stefan Franz, Andrea Müllebner, Gabriela Feurstein, Christina Wagner, Thomas Eder, Tea Pemovska, Christiane Agreiter, Alexander Pichler, Philipp B Staber, Martin Hofer, Ralf Steinborn, Svenja-Verena Strohmer, Ingrid Simonitsch-Klupp, Marcus Bauer, Andreas Wilfer, Thomas Weber, Swapnil Potdar, Tero Aittokallio, Dennis Jungherz, Tony A Müller, Julia List, Dagmar Gotthardt, Florian Grebien, Vasileios Bekiaris, Marco Herling, Richard Moriggl, Heidi A Neubauer","doi":"10.1002/hem3.70345","DOIUrl":"10.1002/hem3.70345","url":null,"abstract":"","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 4","pages":"e70345"},"PeriodicalIF":14.6,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722646","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monocyte-mediated metabolic rewiring via CD31-CD38 interactions promotes growth and drug-resistance in multiple myeloma.","authors":"Ramin Raoof, Giada Dal Collo, Helga Simon-Molas, Panagiota Tzortzi, Konxhe Kulaj, Elif N Demirez, Crescenzo Massaro, Renée Poels, Charlotte L B M Korst, Chloe A O'Neill, Wassilis S C Bruins, Marloes E C Broekmans, Payam Behradkia, Maria Krevvata, Sonja Zweegman, Arnon P Kater, Serena R Baglio, Tuna Mutis, Niels W C J van de Donk","doi":"10.1002/hem3.70358","DOIUrl":"https://doi.org/10.1002/hem3.70358","url":null,"abstract":"<p><p>Multiple myeloma (MM) cells interact with different components of the bone marrow (BM) microenvironment, which plays a critical role in MM progression and confers resistance to therapy. Here, we report that monocytes actively control MM cell metabolism by transferring mitochondria to MM cells, thereby increasing their mitochondrial content. Transfer of mitochondria required the expression of CD38 on the surface of MM cells and its ligand CD31 (PECAM-1) on monocytes. The mitochondrial increase in MM cells induced a boost in oxidative phosphorylation (OXPHOS). This monocyte-mediated metabolic adjustment promoted growth, motility, and drug-resistance in both MM cell lines and primary MM cells. Notably, the CD38-targeting monoclonal antibody daratumumab prevented mitochondrial transfer via blocking CD38 on MM cells. Furthermore, in the presence of daratumumab, monocytes acquired a divergent role and obtained mitochondria from MM cells through the process of trogocytosis. Daratumumab-mediated disruption of mitochondrial transfer reduced the mitochondrial content in MM cells, prevented the boost in OXPHOS, significantly impaired MM cell growth and migration, and mitigated drug-resistance. In conclusion, we reveal a crucial metabolic interplay between monocytes and MM cells within the BM microenvironment that promotes tumor growth and induces therapy resistance, providing the rationale for treatment strategies that combine targeting tumor metabolism with existing anti-MM agents.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 4","pages":"e70358"},"PeriodicalIF":14.6,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13084703/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"APL-like subset within <i>NPM1</i>-mutated AML: A distinct immunophenotype correlating with early vascular complications.","authors":"Francesco Mannelli, Francesca Crupi, Sara Bencini, Michaela Feuring, Gaia Ciolli, Matteo Piccini, Marco Frigeni, Raffaele Palmieri, Chiara Sartor, Barbara Scappini, Giacomo Gianfaldoni, Benedetta Peruzzi, Roberto Caporale, Antonio Scannella, Laura Fasano, Elisa Quinti, Andrea Pasquini, Jessica Caroprese, Leonardo Signori, Fabiana Pancani, Chiara Maccari, Tiziana Ottone, Daniela Spaeth, Antonio Curti, Maria Teresa Voso, Francesco Annunziato, Konstanze Döhner, Adriano Venditti, Francesco Buccisano, Alessandro Rambaldi, Paola Guglielmelli, Hartmut Döhner, Alessandro M Vannucchi","doi":"10.1002/hem3.70307","DOIUrl":"10.1002/hem3.70307","url":null,"abstract":"<p><p>Among <i>NPM1</i>-mutated acute myeloid leukemia (AML) (<i>NPM1</i> ^mut), a distinct subtype has been described with an immunophenotypic profile resembling acute promyelocytic leukemia (APL-like). In this retrospective multicenter study including 384 <i>NPM1</i> ^mut AML patients, we identified 95 (24.7%) cases exhibiting an APL-like immunophenotype. This subset was characterized by significant abnormalities in coagulopathy markers (D-dimer, D-dimer/fibrinogen ratio, and disseminated intravascular coagulation [DIC] score). The cumulative incidence of vascular events at 30 days was significantly higher in the APL-like group compared to the non-APL-like group (30.5% vs. 10.1%, P < 0.001). Notably, a higher cumulative incidence of early death due to vascular complications (within 30 days) was observed in the APL-like group (6.3% vs. 0.35% in controls; P = 0.00015). In multivariate analysis, the APL-like immunophenotype was the only significant factor associated with vascular-related early death (hazard ratio [HR] = 19, P = 0.0063). There was a significantly higher rate of <i>IDH1/2</i> mutations in APL-like (68.3%) compared to non-APL-like (18.3%, P < 0.001) cases. We validated these clinical and molecular findings in an independent validation cohort of 302 <i>NPM1</i> ^mut patients enrolled in the acute myeloid leukemia study group (AMLSG) 09-09 clinical trial, which included the administration of all-trans retinoic acid (ATRA) to all patients and a randomization for gemtuzumab ozogamicin. In this cohort, the APL-like immunophenotype was associated with events occurring within the first 15 days but did not influence mortality, likely due to protocol-driven patient selection. Our findings have important clinical implications that warrant the development of studies exploring disease-tailored clinical measures to mitigate the risk of early vascular events, as in current APL management.</p>","PeriodicalId":12982,"journal":{"name":"HemaSphere","volume":"10 4","pages":"e70307"},"PeriodicalIF":14.6,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13086621/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}