Leukemia最新文献

{"title":"Aberrant expression of MERTK activates BCR via CD79a in CLL cells: alternative therapeutic strategy for relapsed/refractory CLL","authors":"Mariana T. Mendez,Tapojyoti Sanyal,Murali K. Mamidi,Stacey M. Fernandes,Sara K. Vesely,Marek Mraz,Jennifer R. Brown,Jennifer Holter-Chakrabarty,Asish K. Ghosh","doi":"10.1038/s41375-026-03147-2","DOIUrl":"https://doi.org/10.1038/s41375-026-03147-2","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"4 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149022241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C3- and C5-deficient murine cells exhibit severe mitochondrial defects, indicating a pivotal, novel role of innate immunity in regulating hematopoiesis at the electron transfer chain level","authors":"Michalina Kazek,Damian Wojdalski,Adrian Konopko,Patrycja Kieszek,Agnieszka Lukomska,Kannathasan Thetchinamoorthy,Hanna Nieznańska,Magdalena Świadek,Emilia Waraksa-Zasada,Janina Ratajczak,Magdalena Kucia,Mariusz. Z. Ratajczak","doi":"10.1038/s41375-026-03134-7","DOIUrl":"https://doi.org/10.1038/s41375-026-03134-7","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"1 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149020390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incidentally detected vertebral fractures and risk of myeloma: a prospective cohort study of 9059 CT-scanned Danish general population individuals.","authors":"Rasmus Rønnemoes, Anne Rudbeck Juhl, Shoaib Afzal, Stig Egil Bojesen, Børge Grønne Nordestgaard, Michael Huy Cuong Pham, Klaus Fuglsang Kofoed, Jørgen Tobias Kühl, Andreas Fuchs Larsen, Per Ejlstrup Sigvardsen, Thomas S Kristensen, Jesper Petersen, Andreas Glenthøj, Jens Helby","doi":"10.1038/s41375-026-03135-6","DOIUrl":"https://doi.org/10.1038/s41375-026-03135-6","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149001777","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical evaluation of AI-assisted quantitative marrow fibrosis assessment using Continuous Indexing of Fibrosis (CIF).","authors":"Sharon Ruane, Rosalin A Cooper, Carlo Pescia, Neha Bhardwaj, Anna Green, Deborah Hay, Jana Ihlow, Fatima Zahra Jelloul, Rashmi Kanagal-Shamanna, Philip Macklin, Vidhya Manohar, Edoardo Olmeda, Mark Ong, Andres Quesada, Jens Rittscher, Hosuk Ryou, Saad Bashir, Sam Maxwell, Ka Ho Tam, Alan Aberdeen, Len Brandes, Korsuk Sirinukunwattana, Timothy Ebsworth, Daniel Royston","doi":"10.1038/s41375-026-03126-7","DOIUrl":"https://doi.org/10.1038/s41375-026-03126-7","url":null,"abstract":"<p><p>Assessment of fibrosis is central to the evaluation of diagnostic bone marrow trephine (BMT) biopsies. However, manual fibrosis grading is subjective and only semi-quantitative. We evaluated the clinical utility of a previously developed AI-based quantitative fibrosis assessment tool, Continuous Indexing of Fibrosis (CIF), using ~1000 consecutive BMT biopsies without pre-selection. An international panel of 14 haematopathologists performed manual reads using whole-slide images (WSI) of reticulin-stained slides and two types of CIF-assisted reads (Sequential-assisted and Concurrent-assisted) across three study rounds. The AI-derived CIF scores correlated strongly with the manual consensus MF grade (Spearman ρ = 0.770) and demonstrated good discriminative performance across adjacent MF grade boundaries. The CIF-assisted protocols significantly improved intra-observer and inter-observer agreement compared to manual assessment, without increasing read times. Sequential-assisted reads yielded the largest gain in inter-observer agreement (12.6 percentage points; 95% CI 10.5-14.8) and improved agreement with the consensus reference (3.0 percentage points; 95% CI 0.4-5.7). Both assisted protocols reduced discordance across the clinically significant MF-1 / MF-2 boundary. These findings demonstrate that AI-assisted quantitative bone marrow fibrosis assessment using CIF is reproducible, efficient and well suited for future clinical deployment testing. This supports a future role in standardising routine diagnostic haematopathology and enhancing the sensitivity of fibrosis-based clinical trial endpoints.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting CD38 with bispecific antibody XmAb 18968 in patients with relapsed/refractory acute myeloid leukemia and T-cell acute lymphoblastic leukemia.","authors":"Guru Subramanian Guru Murthy, Bijal Shah, Talha Badar, Jessica Leonard, Adam DuVall, Cecilia Arana Yi, Aniko Szabo, Arielle Baim, Alexandra Harrington, Lyndsey Runaas, Karen Carlson, Laura Michaelis, Sameem Abedin, Tyce Kearl, Ehab Atallah","doi":"10.1038/s41375-026-03130-x","DOIUrl":"https://doi.org/10.1038/s41375-026-03130-x","url":null,"abstract":"<p><p>CD38 is a transmembrane glycoprotein highly expressed in acute myeloid leukemia (AML) and T-cell acute lymphoblastic leukemia (T-ALL). XmAb18968 is a novel CD38-CD3 bi-specific T-cell engager with Fc domain modified to reduce non-selective activation of effector cells. In this phase 1 multicenter clinical trial, we evaluated the outcomes of XmAb18968 in adults with relapsed/refractory (RR) AML and T-ALL. Twenty-two patients with AML (n = 13) and T-ALL (n = 9) with a median age of 63 years (range 31-77) were enrolled. Prior lines of therapy (median 3, range 1-8) included venetoclax (77.3%), allogeneic HCT (22.7%), CD7 CAR-T cell therapy and daratumumab (11.1%). Grade ≥3 adverse events included anemia (14%), neutropenia (18%), and thrombocytopenia (14%). No grade ≥3 cytokine release syndrome or neurotoxicity was seen. Overall, 17 patients (AML = 11, ALL = 6) completed at least one cycle of therapy. Among 11 patients with RR-AML, one achieved partial remission (PR) and two achieved MRD negative complete remission (CR). In 6 patients with RR-T-ALL, 4 achieved meaningful improvement in disease burden with 1 clearance of MRD. Median OS was 8.5 months in AML and 8.7 months in T-ALL. XmAb18968 is safe and tolerable with encouraging preliminary efficacy, supporting further investigation of CD38 targeting therapies in this setting (NCT05038644).</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SRSF2 P95H induces monocytic priming of human hematopoietic stem and progenitor cells.","authors":"Johannes Foßelteder, Gabriel Pabst, Andrea Raicht, Tommaso Sconocchia, Angelika Schlacher, Lisa Auinger, Daniel Martinez-Krams, Asiri Ediriwickrema, Katarina Vizar-Cisarova, Peter Schlenke, Annkristin Heine, Heinz Sill, Armin Zebisch, Ravindra Majeti, Andreas Reinisch","doi":"10.1038/s41375-026-03127-6","DOIUrl":"https://doi.org/10.1038/s41375-026-03127-6","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148969541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating tumor cells identify a disseminated genomic high-risk phenotype within IMS-IMWG 2025 staging in newly diagnosed multiple myeloma","authors":"Yating Li, Lihui Shi, Wenqiang Yan, Yuntong Liu, Jian Cui, Jingyu Xu, Jieqiong Zhou, Chenxing Du, Shuhui Deng, Weiwei Sui, Yan Xu, Lugui Qiu, Gang An","doi":"10.1038/s41375-026-03133-8","DOIUrl":"https://doi.org/10.1038/s41375-026-03133-8","url":null,"abstract":"The 2025 IMS-IMWG consensus genomic staging (CGS) system has improved genomic risk stratification in newly diagnosed multiple myeloma (NDMM), yet does not capture whether high-risk clones have acquired a disseminated phenotype. We investigated whether circulating tumor cells (CTC) refine CGS and enable longitudinal residual disease monitoring. We retrospectively analyzed 631 MM patients from the NICHE cohort (NCT04645199) who underwent CTC assessment across disease phases. Among 410 patients assessed at diagnosis, CTC were detectable in 63.9% and correlated with both bone marrow plasma cell infiltration and accumulation of high-risk cytogenetic abnormalities. In 359 NDMM patients with adequate follow-up, a cohort-derived CTC threshold of 0.38% independently predicted inferior progression-free survival (PFS) after multivariable adjustment. Importantly, CTC refined prognostic stratification specifically within the CGS high-risk subgroup. Patients with CGS high-risk/CTC-high disease had the shortest PFS, thereby defining a disseminated genomic high-risk phenotype comprising 12.4% (39/314) of evaluable NDMM patients. In follow-up cohorts, detectable CTC were associated with inferior outcomes in 127 patients assessed during non-progressive disease states, whereas combined CTC and bone marrow minimal residual disease assessment stratified outcomes in 120 patients with paired measurements. Overall, CTC-integrated CGS supports minimally invasive baseline risk stratification and longitudinal disease monitoring.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"15 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148899552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting PI3K decreases trogocytosis-mediated CAR T cell fratricide.","authors":"Tarang Sharma, Maday Galeana Figueroa, Kishan Kumar Nyati, Ravi K Shah, Meera Mohan, Parameswaran Hari, Tim Luetkens, Sabarinath Venniyil Radhakrishnan","doi":"10.1038/s41375-026-03129-4","DOIUrl":"https://doi.org/10.1038/s41375-026-03129-4","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functional characterization of snoRNA-derived RNA (sdRNA) expression in healthy hematopoiesis and acute myeloid leukemia.","authors":"Rafael Zinz, Christian Rohde, Cornelius Pauli, Fengbiao Zhou, Azmal Ali Syed, Daniel Heid, Viral Shah, Niklas Alexander Wahl, Adrija Ray, Simon Renders, Laura Werner, Sandra Förmer, Carl Ahrens, Claudia Baldus, Martin Bornhäuser, Christoph Röllig, Hubert Serve, Tim Sauer, Jeroen Krijgsveld, Carsten Müller-Tidow, Maximilian Felix Blank","doi":"10.1038/s41375-026-03120-z","DOIUrl":"10.1038/s41375-026-03120-z","url":null,"abstract":"<p><p>SnoRNAs are highly expressed in AML and have implications in leukemogenesis and leukemic maintenance. SnoRNAs can be further processed into snoRNA-derived RNAs (sdRNAs). The role of sdRNAs in AML and healthy hematopoiesis remains largely elusive. We characterized sdRNA and snoRNA levels in hematopoietic stem and progenitor cells (HSPCs), healthy WBCs, and 159 intensively treated AML patient samples at initial diagnosis. HSPCs, healthy WBCs, and AML blasts could be differentiated by their sdRNA expression pattern in a cell-type-specific manner. In AML, high sd3'-RNA/snoRNA-host gene ratios were associated with an inverse patient outcome. Particularly, in NPM1-mutated patients with favorable risk stratification and good initial therapy response, high sd3'-RNA ratios identified a subgroup with inferior outcome. High sd3'-RNA ratios were associated with altered oncogenic, inflammatory, and immune response signaling. Forced expression of single sdRNAs, such as sd3'-SNORD78, sd3'-SNORD76, and sd5'-SNORD93, enhanced clonogenic potential in AML and drove sdRNA-specific gene expression signatures in both AML and healthy HSPCs. Exemplarily, we propose and characterize NUDT21, an important regulator of alternative polyadenylation and oncogenic gene expression, as a downstream target of sd3'-SNORD78 in AML. Our data introduce sdRNAs as standalone regulatory effector molecules in healthy hematopoiesis and AML.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Csnk1a1 E98 mutations rewire signaling and metabolism in del(5q) myelodysplastic neoplasms.","authors":"Stephani Schmitz, Juliette E Pearce, Sergio Martinez-Høyer, Gerjanne Vroeg In de Wei, Inge A M Snoeren, Ursula S A Stalmann, Stijn N R Fuchs, Aurelien J F Dugourd, Giulia Franciosa, Eric M Bindels, Wencke Walter, Claudia Meyer, Torsten Haferlach, Emiel P C van der Vorst, Oriol Calvete, Francesc Solé, Julio Saez-Rodriguez, Andreas Linkermann, Jesper Olsen, Hélène F E Gleitz, Rebekka K Schneider","doi":"10.1038/s41375-026-03122-x","DOIUrl":"https://doi.org/10.1038/s41375-026-03122-x","url":null,"abstract":"<p><p>Deletion of chromosome 5q [del(5q)] is the most common cytogenetic abnormality in myelodysplastic neoplasms (MDS) and results in haploinsufficiency of multiple genes, including CSNK1A1. Recurrent CSNK1A1 mutations, predominantly affecting the E98 hotspot, occur almost exclusively in del(5q) MDS and are associated with adverse outcomes, yet their impact on CK1ɑ function remains unclear. Using integrated transcriptomic, (phospho)proteomic, and kinome activity profiling in hematopoietic stem and progenitor cells (HSPCs), combined with in vivo serial transplantation assays, we show that Csnk1a1 E98V represents a change-of-function rather than a loss-of-function mutation. Unlike Csnk1a1 haploinsufficiency, Csnk1a1 E98V preserves long-term hematopoietic reconstitution and does not enhance clonal expansion in vivo. Instead, the mutation induces suppression of kinase signaling networks, leading to coordinated repression of ribosomal gene expression, protein translation, and cell cycle programs. This signaling rewiring is accompanied by metabolic reprogramming characterized by reduced mitochondrial respiration, increased glycolytic flux, and an inability to adapt to metabolic challenges, creating a stress-tolerant but inflexible cellular state. Notably, Csnk1a1 E98V cells exhibit impaired megakaryopoiesis and increased vulnerability to iron overload, as well as RSL-3-mediated ferroptosis. Analysis of del(5q) MDS patients confirmed that CSNK1A1 mutations are associated with distinct clinical features, including thrombocytopenia, elevated myeloblasts, and reduced bone marrow iron levels. Together, our findings support a two-step model in which del(5q)-associated CSNK1A1 haploinsufficiency drives clonal expansion, followed by acquisition of CSNK1A1 mutations that promote stress tolerance rather than increased proliferation. This adaptive rewiring exposes metabolic and iron-dependent vulnerabilities that may be therapeutically exploited.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887804","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}