Leukemia最新文献

{"title":"Correction: BCR::ABL1 tyrosine kinase inhibitors induce ribosome collisions to activate ZAK-dependent ribotoxic stress and apoptosis in chronic myeloid leukemia.","authors":"Jumin Park, Soo-Hyun Kim, Jongmin Park, Heeju Park, Hongtae Kim, Dong-Wook Kim, Chunghun Lim","doi":"10.1038/s41375-026-03166-z","DOIUrl":"https://doi.org/10.1038/s41375-026-03166-z","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148137","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":"Bone health in myelodysplastic neoplasms: results from the prospective longitudinal BoHemE study.","authors":"Heike Weidner, Elena Tsourdi, Anne Sophie Platzbecker, Martina Rauner, Ulrike Baschant, Maria G Ledesma-Colunga, Karolina Basiak, Katja Sockel, Ekaterina Balaian, Susann Winter, Anna Harig, Klaus H Metzeler, Katharina S Götze, Dominic Brauer, Nicole Modler, Michael Cross, Marie Schneider, Jörg Lützner, Andreas Roth, Thomas Zerjatke, Gabriele Müller, Uwe Platzbecker, Lorenz C Hofbauer","doi":"10.1038/s41375-026-03125-8","DOIUrl":"https://doi.org/10.1038/s41375-026-03125-8","url":null,"abstract":"<p><p>Myelodysplastic neoplasms (MDS) are characterized by insufficient hematopoiesis and alterations of the bone marrow microenvironment. However, bone health in MDS has not been evaluated in a prospective, longitudinal setting. Within the Bone and Hematology in Elderly (BoHemE) study, bone mineral density (represented as T-score) and bone-specific serum markers were assessed in patients with MDS (n = 111; 36% female) and age-matched controls (n = 84; 55% female) at baseline and after 3 years. At baseline, patients with MDS had a lower T-score [-0.2; p < 0.05] compared to controls, which was mainly attributed to the lower T-score in women with MDS [-0.3; p < 0.05]. Furthermore, the DNMT3A mutation was associated with a lower T-score within the MDS cohort [-0.7; p < 0.05], but the occurrence in controls had no effect. Albumin-adjusted calcium and phosphate levels correlated with T-scores within the MDS cohort [p < 0.0001 and p < 0.01, respectively], independent of age, sex, MDS duration, IPSS-M score, or transfusion dependence. Quality of life was lower in patients with MDS [p < 0.01], and remained stable over 3 years, whereas T-scores declined [-0.3; p < 0.05]. The presence of osteoporosis was associated with poor overall survival in MDS [p < 0.01]. In conclusion, bone health should be evaluated as part of the diagnostic work-up and clinical management of MDS.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148051","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":"Mitochondria transfer via tunneling nanotubes drives macrophage immunosuppression and metabolic reprogramming in pediatric AML.","authors":"Alicia Perzolli, Farah Massaoudi, Anita T van Oort, Joost B Koedijk, Elizabeth K Schweighart, Lennart A Kester, Fabienne Adriaanse, Kimberly Smit, Wilbert P Vermeij, Bianca F Goemans, Josef Vormoor, C Michel Zwaan, Olaf Heidenreich","doi":"10.1038/s41375-026-03164-1","DOIUrl":"https://doi.org/10.1038/s41375-026-03164-1","url":null,"abstract":"<p><p>Although immunotherapy has revolutionized cancer treatment, its benefits in pediatric acute myeloid leukemia (AML) remain limited, partly due to an incomplete understanding of the AML microenvironment. While most studies focus on T cells, innate immune populations such as macrophages are less well explored. In pediatric AML patients, we demonstrate that immunosuppressive macrophages dominate the AML microenvironment and support growth of RUNX1::RUNX1T1 and KMT2A-rearranged leukemic blasts. In co-culture experiments, AML cells reprogrammed naïve and pro-inflammatory macrophages toward an anti-inflammatory state, characterized by suppression of NF-κB and other inflammatory pathways. This phenotypic switch requires direct cell contact and involves tunneling nanotube-mediated transfer of AML mitochondria to macrophages associated with metabolic rewiring toward oxidative phosphorylation. Functionally, these reprogrammed macrophages exhibited impaired phagocytosis, convey chemoresistance and reduced T cell- and bispecific antibody-mediated killing, facilitating immune escape. Our findings reveal a novel mechanism of immune suppression and suggest that targeting AML-macrophage interactions could enhance the efficacy of T cell-based immunotherapies.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149883","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":"Predicting the clinical course of advanced systemic mastocytosis on treatment with avapritinib or midostaurin.","authors":"Johannes Lübke, Jason Gotlib, Daniel J DeAngelo, Juliana Schwaab, Deepti H Radia, Michael Deininger, Tracy I George, Ilda Bidollari, Saša Dimitrijević, Javier I Muñoz-González, Hongliang Shi, Andreas Reiter","doi":"10.1038/s41375-026-03149-0","DOIUrl":"https://doi.org/10.1038/s41375-026-03149-0","url":null,"abstract":"<p><p>Advanced systemic mastocytosis (AdvSM) is driven by KIT D816V in approximately 95% of cases. Accurate assessment and prediction of clinical course and disease outcome before and during treatment with the KIT inhibitors midostaurin and avapritinib may facilitate optimization of treatment strategies. We retrospectively evaluated clinical, morphologic, laboratory, and genetic predictors of outcome in 79 midostaurin- and 176 avapritinib-treated patients. The number of mutations at baseline in SRSF2/ASXL1/EZH2 (midostaurin) and in SRSF2/RUNX1/SETBP1 (avapritinib) delineated highly predictive 3-tier risk classification systems. Treatment with avapritinib was associated with an early response of the KIT D816V variant allele frequency; a ≥10% reduction in peripheral blood at day 15 indicated improved overall survival (OS). Within 3 months of starting treatment, a ≥25% increase in alkaline phosphatase (AP) levels (AP flare) was observed in 46/47% of midostaurin/avapritinib-treated patients and was associated with longer OS. Multivariable analyses identified a ≥25% reduction in the KIT D816V allele burden (midostaurin), normalization of serum albumin levels (avapritinib), and normalization of hemoglobin and/or platelet levels (midostaurin and avapritinib) within 6 months as significant predictors for prolonged OS. In conclusion, genetic profiling, dynamic laboratory parameters, and KIT D816V monitoring improve outcome prediction in patients with AdvSM on midostaurin or avapritinib.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149147656","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":"RUNX1 aberrations in blast-phase chronic myeloid leukaemia induce the RNA-binding protein SPATS2L, which promotes growth, survival and stress granule assembly.","authors":"D A Palmer, D Ogilvie-Park, A L Muir, R Craig, O Sevim, L Stott, A Kakkar, P A Lewis, M Wilson, K Heesom, G A Horne, M Copland, S Mustjoki, S Adnan-Awad, K Porkka, S Jain, N Bayat, D Famili, H Webb, M J West, F K Mardakheh, T Chevassut, A Tonks, S G Kellaway, B P Towler, R G Morgan","doi":"10.1038/s41375-026-03161-4","DOIUrl":"https://doi.org/10.1038/s41375-026-03161-4","url":null,"abstract":"<p><p>RUNX1 is a critical regulator of hematopoiesis. In CML, somatic RUNX1 mutations and RUNX1::MECOM/EVI1, are associated with TKI resistance and progression to BP-CML. To examine post-transcriptional dysregulation downstream of RUNX1 aberrations, we used orthogonal organic phase separation to characterise the RNA-binding proteome of RUNX1 deficient BP-CML cells. RUNX1 depleted BP-CML cells exhibited significant alterations to RBPs involved in stress response pathways and translation/ribosome-biogenesis. Furthermore, RUNX1 depletion or expression of RUNX1::EVI1 in BP-CML cells induced expression and RNA binding activity of SPATS2L, a component of stress granules (SG). Whilst RUNX1 depletion increased SG-assembly, SPATS2L depletion reduced SG-assembly and inhibited the growth/survival of multiple BP-CML cell lines. Homoharringtonine (HHT), used historically in TKI-resistant CML, ablated SG-assembly in BP-CML cells with RUNX1 depletion, and primary BP-CML cells with LOF/hypomorphic RUNX1 mutations were preferentially sensitised to HHT. Suppressing SPATS2L expression induced by RUNX1 depletion, reduced SG-forming capacity and increased the HHT-sensitivity of RUNX1 depleted BP-CML cells, suggesting SPATS2L contributes to therapeutic resistance in RUNX1 mutated CML. Finally, we demonstrate that SGs may contribute more widely to TKI-resistance in this setting. This study suggests that SPATS2L/SG induction could be critical to RUNX1-mutant leukemias, and, provides preliminary evidence for a mutationally-targeted approach in CML with RUNX1 aberrations.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149148428","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":"Novel RNA polymerase I and cyclin-dependent kinase combination therapy for the treatment of aggressive acute myeloid leukemia.","authors":"Nadine Hein, Perlita Poh, Jason A Powell, Lorena Núñez Villacís, Sarah Sant'Anna Maranhão, Maurits Evers, Jirawas Sornkom, Victoria S Pope, Priscilla Soo, Adria Closa, Jasmina Frawley, Sheren J Al-Obaidi, Cathryn M Gould, Piyush Madhamshettiwar, Kaylene J Simpson, Vijay Bhoopalan, Dani Tutuka, Stuart M Pitson, Luc Furic, Konstantin Panov, Katherine M Hannan, Amee J George, Ross D Hannan, Rita Ferreira","doi":"10.1038/s41375-026-03148-1","DOIUrl":"https://doi.org/10.1038/s41375-026-03148-1","url":null,"abstract":"<p><p>Despite advances in therapy, specific subtypes of Acute Myeloid Leukemia (AML) remain largely incurable. The small molecule drug CX-5461 exhibits dual target specificity, acting as a first-in-class ribosome biogenesis inhibitor to induce the nucleolar surveillance pathway (NSP), as well as to poison Topoisomerase IIα (TOPIIA) to induce DNA damage. We conducted a phenotypic screen of FDA-approved drugs to identify compounds that synergies with CX-5461 to enhance the therapeutic efficacy of this drug in incurable AML. The pan-CDK inhibitors Dinaciclib and Flavopiridol were identified as efficient combinatorial therapies with CX-5461. Dinaciclib acts synergistically across a genetically divergent panel of human AML cell lines, significantly improves survival in murine AML models, and reduces colony formation in primary human AML samples. Synergy was attributable, at least partially, to combinatorial activation of the NSP. Both agents independently stabilized p53 but produced distinct biological outcome; Dinaciclib driving rapid apoptosis and CX-5461 primarily promoting cell-cycle arrest; which together yielded efficient tumor clearance and delayed onset of therapy resistance. These findings provide strong evidence that a combination treatment strategy that leverages nucleolar stress and cell cycle control to enhance treatment outcomes in AML, paving the way for clinical translation of Pol I-CDK co-targeting therapies.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137383","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":"Generation of a novel knock-in mouse line expressing oncogenic Kit D814V in the hematopoietic stem cell compartment as a preclinical model for systemic mastocytosis.","authors":"Simona Stivala, Alina Makeeva, Tiago Almeida Fonseca, Elena Ratti, Etnik Sheremeti, Laetitia Clauss, Marc Usart, Ewelina M Bartoszek, Pawel Pelczar, Martina Konantz, Karin Hartmann","doi":"10.1038/s41375-026-03141-8","DOIUrl":"https://doi.org/10.1038/s41375-026-03141-8","url":null,"abstract":"<p><p>Research in mastocytosis, characterized by clonal expansion of mast cells (MC), and driven by the KIT D816V mutation in >90% of patients, has been hampered by the lack of in vivo models. Here, we describe a novel knock-in mouse line expressing Kit D814V (murine homolog to human KIT D816V) in the hematopoietic compartment by Scl-CreER-mediated recombination. Scl-Cre;Kit^{D814V fl/+} mice presented increased MC progenitors in the bone marrow (BM) leading to MC expansion in the skin, stomach, spleen and liver, and increased serum levels of murine MC protease-1 (mMCP-1) and mMCP-6. Additionally, mice exhibited a myeloid neoplasm with leukocytosis, erythrocytosis, extramedullary hematopoiesis, and hepatosplenomegaly. In competitive BM transplantation, Kit D814V cells had a proliferative advantage over wild-type cells, resulting in increased MC, leukocytosis, erythrocytosis, and extramedullary hematopoiesis in recipient mice. Treatment of transplanted mice with a KIT-targeting tyrosine kinase inhibitor was able to control the mutant clone, and led to significant reduction of skin MC, leukocytes as well as reticulocytes, and normalization of spleen weight. In conclusion, we describe here a novel mouse model presenting a phenotype closely resembling human systemic mastocytosis with associated hematologic neoplasm (SM-AHN), which could help in clarifying the pathogenesis of mastocytosis and exploring novel therapeutic strategies.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137372","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":"Measurable residual disease assessment as an early end point of treatment efficacy in acute myeloid leukemia: a multinational PETHEMA study of 2623 patients treated with intensive therapy.","authors":"Bruno Paiva, Leire Burgos, Carmen Gonzalez, Asmae Ahdadi, Rebeca Rodriguez-Veiga, Antonio Solana-Altabella, Pilar Lloret-Madrid, Evelyn Acuña-Cruz, Cristina Gil, Carmen Botella, Eduardo Rodriguez-Arboli, Teresa Caballero Velazquez, Teresa Bernal, Teresa Cedena, Pilar Herrera, Claudia Lucia Sossa, Josefina Serrano, Joaquin Sanchez, Jose Luis Lopez, Belen Vidriales, Mar Tormo, Monica Alejandra Romero, Mercedes Colorado, Celina Benavente, Juan M Bergua, Manuel Perez-Encinas, Lorenzo Algarra, Carlos Rodriguez-Medina, Dolly Fiallo-Suárez, Raimundo Garcia-Boyero, Luis Felipe Casado, Jorge Labrador, Manuel Barrios, Beatriz de Rueda, Marcela Espinoza, Maria Jose Sayas, Diana Marcela Cuervo, Maria Luz Amigo, Jose Mario Mariz, Karoll Giovanna Gomez, Carmen Couto, Esther Perez, Agatha Almela, Jordi Viñas-Noguera, Esperanza Lavilla-Rubira, Olga Arce, Mayte Olave, Miguel Lopez, Maria Dolores Madrigal, Lara Maria Gomez, Sofia Grille, Sebastian Hidalgo, Daniel Garcia, Maria Jose Garcia, Carmen Martinez, Olga Salamero, Amparo Sempere, Beatriz Martin-Herreros, Armando V Mena, David Martinez-Cuadron, Pau Montesinos","doi":"10.1038/s41375-026-03153-4","DOIUrl":"https://doi.org/10.1038/s41375-026-03153-4","url":null,"abstract":"<p><p>Measurable residual disease (MRD) is an early endpoint of treatment efficacy in some hematological malignancies, but several questions remain unanswered to endorse its use in acute myeloid leukemia (AML). We leveraged PETHEMA real-world outcomes of 2623 newly-diagnosed AML patients fit for intensive therapy and in complete remission (CR) after one cycle, to investigate if MRD assessment using flow cytometry is more sensitive than morphological CR, what is the optimal MRD cutoff, the individual-patient-level association between MRD negative CR and overall survival (OS), and if MRD negative rates after different induction regimens associate with different OS. MRD was detected in 68% of patients and presence of MRD levels ≥0.01-<0.1% associated with inferior OS. MRD negative CR using the 0.01% cutoff showed independent prognostic value and was significantly correlated with OS at the individual patient-level (Global odds ratio 1.23; 95% CI, 1.02-1.40). However, significance was lost in specific subgroups defined by genetic risk and post-consolidation treatment. The relationship between treatment effect in MRD negative CR rates and OS after different induction regimens was generally observed. Altogether, these results support formal studies to investigate the role of MRD as an early endpoint of treatment efficacy in specific subgroups of AML patients.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137353","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":"HMGA1 and HMGA2: epigenetic regulators in myeloproliferative neoplasms and novel platelet transcriptomic biomarkers of myelofibrosis","authors":"Li Z. Luo,Leslie Cope,Zanshé Thompson,Anandi Krishnan,Yuze Du,Bailey West,Tania Jain,Jerry Spivak,Linda Resar","doi":"10.1038/s41375-026-03138-3","DOIUrl":"https://doi.org/10.1038/s41375-026-03138-3","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"26 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088463","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":"Correction: spatial remodeling of bone marrow architecture defines tissue-state signatures of disease activity and therapeutic response in myelodysplastic neoplasms","authors":"Ryan Nachman,Aleksandra Kopacz,Caitlin Unkenholz,Jiani Chai,Arvin Ruiz,Itzel Valencia,Jeanne Jiang,Fabio Socciarelli,Jiwoon Park,Christopher E. Mason,Ling Zhang,David Sallman,Gail J. Roboz,Pinkal Desai,Justin Kaner,Joshua Fein,Monica Guzman,Neal Lindeman,Amy Chadburn,Madhu Ouseph,Paul Simonson,Julia Geyer,Giorgio Inghirami,Shahin Rafii,David Redmond,Sanjay S. Patel","doi":"10.1038/s41375-026-03090-2","DOIUrl":"https://doi.org/10.1038/s41375-026-03090-2","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"24 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149088435","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}