Leukemia最新文献

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The complosome - a key regulator of hematopoietic stem cells and innate immune responses 复合体-造血干细胞和先天免疫反应的关键调节因子
IF 13.4 1区 医学
Leukemia Pub Date : 2025-08-13 DOI: 10.1038/s41375-025-02728-x
Henning Ulrich
{"title":"The complosome - a key regulator of hematopoietic stem cells and innate immune responses","authors":"Henning Ulrich","doi":"10.1038/s41375-025-02728-x","DOIUrl":"10.1038/s41375-025-02728-x","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 9","pages":"2297-2298"},"PeriodicalIF":13.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144825454","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}
引用次数: 0
Clinically associated genomic landscape of pediatric non-Down Syndrome acute megakaryoblastic leukemia in Chinese patients 中国儿童非唐氏综合征急性巨核细胞白血病临床相关基因组图谱
IF 13.4 1区 医学
Leukemia Pub Date : 2025-08-11 DOI: 10.1038/s41375-025-02741-0
Kefei Wu, Hui Liu, Wenting Hu, Yuhan Liu, Wenyan Wu, Bowen Cui, Han Wang, Shuang Zhao, Yanjing Tang, Jiaoyang Cai, Yong Wang, Xiang Wang, Xiaoxiao Chen, Yixiao Mo, Ting Liu, Yangyang Xie, Huiying Sun, Ying Zhong, Jianan Rao, Rongrong Fan, Ying Wang, Changcheng Chen, Zhuo Wang, Ronghua Wang, Yuanlu Huang, Qiaoqiao Shi, Lan Wang, Jing Chen, Jing Chen, Benshang Li, Xiaolong Chen, Yu Liu, Shuhong Shen
{"title":"Clinically associated genomic landscape of pediatric non-Down Syndrome acute megakaryoblastic leukemia in Chinese patients","authors":"Kefei Wu, Hui Liu, Wenting Hu, Yuhan Liu, Wenyan Wu, Bowen Cui, Han Wang, Shuang Zhao, Yanjing Tang, Jiaoyang Cai, Yong Wang, Xiang Wang, Xiaoxiao Chen, Yixiao Mo, Ting Liu, Yangyang Xie, Huiying Sun, Ying Zhong, Jianan Rao, Rongrong Fan, Ying Wang, Changcheng Chen, Zhuo Wang, Ronghua Wang, Yuanlu Huang, Qiaoqiao Shi, Lan Wang, Jing Chen, Jing Chen, Benshang Li, Xiaolong Chen, Yu Liu, Shuhong Shen","doi":"10.1038/s41375-025-02741-0","DOIUrl":"10.1038/s41375-025-02741-0","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2533-2537"},"PeriodicalIF":13.4,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144819213","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}
引用次数: 0
Towards methylation-based redefinition of TAL1 positive T-cell acute lymphoblastic leukaemia (T-ALL) 基于甲基化的TAL1阳性t细胞急性淋巴细胞白血病(T-ALL)的重新定义
IF 13.4 1区 医学
Leukemia Pub Date : 2025-08-08 DOI: 10.1038/s41375-025-02714-3
Charlotte Smith, Guillaume Charbonnier, Mathieu Simonin, Estelle Balducci, Thomas Steimle, Guillaume P. Andrieu, Agata Cieslak, Marianne Courgeon, Marc LeLorc’h, Anand Mayakonda, Christoph Plass, Aurélie Le Nezet, Mehdi Latiri, Norbert Ifrah, Hervé Dombret, Françoise Huguet, André Baruchel, Elizabeth Macintyre, Arnaud Petit, Nicolas Boissel, Vahid Asnafi, Aurore Touzart
{"title":"Towards methylation-based redefinition of TAL1 positive T-cell acute lymphoblastic leukaemia (T-ALL)","authors":"Charlotte Smith, Guillaume Charbonnier, Mathieu Simonin, Estelle Balducci, Thomas Steimle, Guillaume P. Andrieu, Agata Cieslak, Marianne Courgeon, Marc LeLorc’h, Anand Mayakonda, Christoph Plass, Aurélie Le Nezet, Mehdi Latiri, Norbert Ifrah, Hervé Dombret, Françoise Huguet, André Baruchel, Elizabeth Macintyre, Arnaud Petit, Nicolas Boissel, Vahid Asnafi, Aurore Touzart","doi":"10.1038/s41375-025-02714-3","DOIUrl":"10.1038/s41375-025-02714-3","url":null,"abstract":"TAL1 is one of the most frequently dysregulated oncogenes in T-cell Acute Lymphoblastic Leukaemia (T-ALL). However, the precise frequency and prognostic impact associated with its dysregulation remains unclear and is confounded by TAL1’s diverse dysregulation mechanisms. TAL1 dysregulation is detected by TAL1 transcript quantification, though this technique may be subject to interference by TAL1 transcripts deriving from residual haematological cells that physiologically express high levels of the gene. We hypothesised TAL1 DNA methylation could provide a more reliable biomarker than TAL1 transcript quantification alone. We extensively studied TAL1 dysregulation in a large adult and paediatric T-ALL cohort (n = 401) and designed a TAL1 specific MS-MLPA assay to determine methylation levels. Whereas monoallelic TAL1 + T-ALL had homogeneous gene expression profiles, never expressed other driver oncogenes and were TAL1 hypomethylated (methylation ratio <0.4), biallelic TAL1 + T-ALL were enriched in expression of other driver oncogenes (TLX1, TLX3, HOXA), and had heterogeneous transcriptomes and TAL1 methylation levels. In PDX analysis, monoallelic TAL1 expression was stable, contrary to biallelic expression which mostly derived from residual non-malignant haematopoietic cells. Importantly, we report 5 novel TAL1 dysregulation mechanisms using long-read nanopore and OGM analysis, and show that TAL1 hypomethylation identifies TAL1 dysregulation, and is associated with worse prognosis.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2344-2354"},"PeriodicalIF":13.4,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797043","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}
引用次数: 0
The histone-methyltransferase DOT1L cooperates with LSD1 to control cell division in blast-phase MPN 组蛋白甲基转移酶DOT1L与LSD1协同控制胚期MPN细胞分裂
IF 13.4 1区 医学
Leukemia Pub Date : 2025-08-08 DOI: 10.1038/s41375-025-02719-y
Karl Kapahnke, Thomas Plenge, Tabea Klaus, Manoj K. Gupta, Disha Anand, Tamer T. Önder, Birgit Perner, Tina M. Schnöder, Felicitas R. Thol, Frederik Damm, Florian H. Heidel, Florian Perner
{"title":"The histone-methyltransferase DOT1L cooperates with LSD1 to control cell division in blast-phase MPN","authors":"Karl Kapahnke, Thomas Plenge, Tabea Klaus, Manoj K. Gupta, Disha Anand, Tamer T. Önder, Birgit Perner, Tina M. Schnöder, Felicitas R. Thol, Frederik Damm, Florian H. Heidel, Florian Perner","doi":"10.1038/s41375-025-02719-y","DOIUrl":"10.1038/s41375-025-02719-y","url":null,"abstract":"Persistence of JAK2-mutated clones that may undergo clonal evolution and malignant transformation remains a challenge in myeloproliferative neoplasms (MPN), Novel therapeutic approaches to attenuate clonal evolution and progression to blast-phase are therefore urgently needed. LSD1 (KDM1A) inhibitors reduce symptoms and clonal burden in MPN, but whether these compounds may be effective in advanced disease stages remained so far elusive. Using a chromatin-focused CRISPR-Cas9 screen, we identified the histone methyltransferase DOT1L as a synthetic lethal target under pharmacologic LSD1 inhibition. DOT1L knockout impaired cellular fitness, reduced proliferation, and prolonged survival in xenografts. Furthermore, genetic inactivation of DOT1L increased LSD1 inhibitor sensitivity up to 100-fold resulting in cell cycle arrest and apoptosis induction in TP53 mutant blast-phase MPN. Mechanistically, we have identified a novel, non-canonical function of DOT1L which co-occupied LSD1-bound enhancers and contributed to the repression of transcriptional programs independent of its enzymatic activity. DOT1L loss cooperated with LSD1 inhibitors to activate tumor suppressive programs, while pharmacologic inhibition of DOT1Ls catalytic activity failed to elicit comparable effects. These findings indicate that leveraging DOT1L targeting via protein degradation or RNA interference, rather than conventional enzymatic inhibition, could enhance the therapeutic efficacy of LSD1 inhibitors in blast-phase MPN.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2406-2418"},"PeriodicalIF":13.4,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02719-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Simultaneous whole-body multi-parametric 2-[18F]FDG-PET/MRI in smoldering multiple myeloma assessment: diagnostic and prognostic impact 同时全身多参数2-[18F]FDG-PET/MRI在阴燃型多发性骨髓瘤评估中的应用:诊断和预后影响
IF 13.4 1区 医学
Leukemia Pub Date : 2025-08-07 DOI: 10.1038/s41375-025-02717-0
Bastien Jamet, Cyrille Touzeau, Hatem Necib, Éric Frampas, Huajun Sun, Chloe Francois, Nicolas Blin, Thomas Carlier, Aurélien Monnet, Nicoletta Lilli, Caroline Bodet-Milin, Philippe Moreau, Françoise Kraeber-Bodere
{"title":"Simultaneous whole-body multi-parametric 2-[18F]FDG-PET/MRI in smoldering multiple myeloma assessment: diagnostic and prognostic impact","authors":"Bastien Jamet, Cyrille Touzeau, Hatem Necib, Éric Frampas, Huajun Sun, Chloe Francois, Nicolas Blin, Thomas Carlier, Aurélien Monnet, Nicoletta Lilli, Caroline Bodet-Milin, Philippe Moreau, Françoise Kraeber-Bodere","doi":"10.1038/s41375-025-02717-0","DOIUrl":"10.1038/s41375-025-02717-0","url":null,"abstract":"The co-primary aims of this study were to assess the diagnostic and prognostic performance of Whole-body-2-[18F]-fluorodeoxyglucose-positron emission tomography coupled with MRI (WB-2-[18F]FDG-PET/MRI) imaging in the smoldering multiple myeloma (SMM) workup for detection of MM-related medullary or extra-medullary disease and for the prediction of progression-free survival (PFS) defined as time to progression to symptomatic MM requiring therapy. A total of 116 patients with SMM (without CRAB or SLiM criteria before imaging) were prospectively included in the study and underwent full multi-parametric WB-2-[18F]FDG-PET/MRI imaging. PET detected at least one FL > 5 mm in 9% of patients compared to 20% on MRI (p = 0.02). PET detected diffuse bone marrow involvement (BMI) in 20% of patients and MRI in 53% (p < 10−3). A total of 98 patients with true SMM not requiring treatment were then followed up. The presence of diffuse BMI on MRI was the strongest adverse prognostic parameter for PFS (univariate: hazard ratio (HR), 6.12; p < 10−2. Multivariate : HR, 4.16; p = 0.03) and could be proposed as a new high-risk biomarker for progression to symptomatic MM. Dynamic contrast-enhanced (DCE)-MRI based increased peak enhancement intensity (PEI) and maximum intensity time ratio (MITR) values were other strong adverse prognostic factors.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2516-2522"},"PeriodicalIF":13.4,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144796862","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}
引用次数: 0
Young unrelated donors confer a survival advantage for patients with myeloid malignancies compared to older siblings 与年长的兄弟姐妹相比,年轻的非亲属供体赋予骨髓恶性肿瘤患者生存优势
IF 13.4 1区 医学
Leukemia Pub Date : 2025-08-06 DOI: 10.1038/s41375-025-02724-1
Johannes Schetelig, Henning Baldauf, Carina Rave, Gesine Bug, Lutz P. Müller, Eva Maria Wagner-Drouet, Francis Ayuketang Ayuk, Wolfgang Bethge, Matthias Stelljes, Thomas Schroeder, Friedrich Stölzel, Edgar Jost, Christoph Schmid, Desiree Kunadt, Katja Sockel, Katharina Egger-Heidrich, Jan Moritz Middeke, Daniel Fürst, Daniel Schefzyk, Jürgen Sauter, Alexander H. Schmidt, Katharina Fleischhauer, Martin Bornhäuser, on behalf of the German Cooperative Transplant Study Group, Deutsches Register für hämatopoetische Stammzelltransplantation und Zelltherapie (DRST)
{"title":"Young unrelated donors confer a survival advantage for patients with myeloid malignancies compared to older siblings","authors":"Johannes Schetelig, Henning Baldauf, Carina Rave, Gesine Bug, Lutz P. Müller, Eva Maria Wagner-Drouet, Francis Ayuketang Ayuk, Wolfgang Bethge, Matthias Stelljes, Thomas Schroeder, Friedrich Stölzel, Edgar Jost, Christoph Schmid, Desiree Kunadt, Katja Sockel, Katharina Egger-Heidrich, Jan Moritz Middeke, Daniel Fürst, Daniel Schefzyk, Jürgen Sauter, Alexander H. Schmidt, Katharina Fleischhauer, Martin Bornhäuser, on behalf of the German Cooperative Transplant Study Group, Deutsches Register für hämatopoetische Stammzelltransplantation und Zelltherapie (DRST)","doi":"10.1038/s41375-025-02724-1","DOIUrl":"10.1038/s41375-025-02724-1","url":null,"abstract":"Donor age is one factor to optimize allogeneic hematopoietic cell transplantation (alloHCT). Therefore, we investigated whether young unrelated donors (UD) provide a benefit for older patients with myeloid malignancies compared to HLA-identical sibling donors (MSD). We performed a retrospective registry study on patients ≥50 years who received a first alloHCT between 2010 and 2020. We compared event-free survival (EFS) of patients who were transplanted from MSD aged ≥50 years versus UD aged ≤35 years who were HLA-compatible for HLA-A, -B, -C, and -DRB1. In total, we analyzed data from 3460 patients. With multivariable adjustment EFS (HR 0.86, p = 0.003), OS (HR 0.82, p < 0.001), and risk of relapse (HR 0.84, p = 0.018) were significantly better for HLA-compatible UD compared to MSD. No survival advantage was found, when UD with unfavorable sex or CMV constellation were compared to MSD with favorable constellations. In a meta-analysis on 9905 patients with myeloid malignancies, including ours, we found reduced risk of relapse (pooled HR 0.78, p = 0.006) and better EFS (pooled HR 0.89, p < 0.001) for young matched UD versus MSD. To select young HLA-compatible UD over older MSD may reduce relapse risk and improve survival for older patients with myeloid malignancies.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2523-2532"},"PeriodicalIF":13.4,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02724-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A novel chimeric antigen receptor T-cell therapy targeting CD84 for the treatment of acute myeloid and T-cell lymphoblastic leukemias 靶向CD84的新型嵌合抗原受体t细胞疗法治疗急性髓细胞和t淋巴细胞白血病
IF 13.4 1区 医学
Leukemia Pub Date : 2025-08-06 DOI: 10.1038/s41375-025-02705-4
Lorena Pérez-Amill, Mercedes Armand-Ugón, Maria Val-Casals, Beatriz Martín-Herreros, José R. Álamo, Sergio Peña, Gerard Frigola, Ane Altuna, Claudio Santos, Francesca Guijarro, Alfredo Minguela, Àlex Bataller, Berta Casanovas-Albertí, Mireia Uribe-Herranz, Irene Navarro, Manuel Guerreiro, Diego Sánchez-Martínez, Néstor Tirado, Talía Velasco-Hernandez, Pablo Menéndez, Antonio Martínez, Montse Rovira, Dolors Colomer, E. Azucena González-Navarro, Jordi Esteve, Álvaro Urbano-Ispizua, Pau Montesinos, Julio Delgado, Manel Juan, Nela Klein-González
{"title":"A novel chimeric antigen receptor T-cell therapy targeting CD84 for the treatment of acute myeloid and T-cell lymphoblastic leukemias","authors":"Lorena Pérez-Amill, Mercedes Armand-Ugón, Maria Val-Casals, Beatriz Martín-Herreros, José R. Álamo, Sergio Peña, Gerard Frigola, Ane Altuna, Claudio Santos, Francesca Guijarro, Alfredo Minguela, Àlex Bataller, Berta Casanovas-Albertí, Mireia Uribe-Herranz, Irene Navarro, Manuel Guerreiro, Diego Sánchez-Martínez, Néstor Tirado, Talía Velasco-Hernandez, Pablo Menéndez, Antonio Martínez, Montse Rovira, Dolors Colomer, E. Azucena González-Navarro, Jordi Esteve, Álvaro Urbano-Ispizua, Pau Montesinos, Julio Delgado, Manel Juan, Nela Klein-González","doi":"10.1038/s41375-025-02705-4","DOIUrl":"10.1038/s41375-025-02705-4","url":null,"abstract":"Despite the remarkable clinical successes of chimeric antigen receptor (CAR) T-cell therapies in treating B-cell malignancies and multiple myeloma, similar outcomes have not been achieved in other indications. For patients with relapsed or refractory (R/R) acute myeloid leukemia (AML) or T-cell acute lymphoblastic leukemia (T-ALL), treatment options are limited, yet CART-cell therapies offer significant potential to address this unmet need. Here, we introduce a first-in-class CART-cell therapy targeting CD84, a novel antigen, for the treatment of R/R AML and T-ALL. CD84 is highly expressed on leukemic blasts, with limited expression on hematopoietic stem progenitor cells (HSPC), and is largely absent in healthy human tissues. Our second-generation CARTs targeting CD84 (CART84) demonstrate potent cytotoxicity against AML and T-ALL cells both in vitro and in vivo in patient-derived xenograft (PDX) models. Furthermore, CART84 eliminated primary leukemic blasts while exhibiting low cytotoxicity against CD34+ HSPC in vitro and in humanized mouse models in vivo, suggesting a low risk of myelotoxicity. These results support CD84 as a promising target for AML and T-ALL and provide the foundation for our upcoming first-in-human phase I/II clinical trial using CD84-directed CAR T cell therapy for patients with R/R AML and T-ALL (EudraCT 2024-519966-31-00).","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2432-2441"},"PeriodicalIF":13.4,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02705-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786490","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Association of the composition of the bone marrow tumor microenvironment in BCR::ABL1-negative myeloproliferative neoplasms with IFN-γ signaling and driver mutations BCR:: abl1阴性骨髓增生性肿瘤中骨髓肿瘤微环境组成与IFN-γ信号和驱动突变的关系
IF 13.4 1区 医学
Leukemia Pub Date : 2025-08-05 DOI: 10.1038/s41375-025-02706-3
Marcus Bauer, Christoforos Vaxevanis, Nadja Jaekel, Hubert Hackl, Andreas Wilfer, Clara Zoellig, Monika Haemmerle, Carsten Müller-Tidow, Haifa Kathrin Al-Ali, Barbara Seliger, Claudia Wickenhauser
{"title":"Association of the composition of the bone marrow tumor microenvironment in BCR::ABL1-negative myeloproliferative neoplasms with IFN-γ signaling and driver mutations","authors":"Marcus Bauer, Christoforos Vaxevanis, Nadja Jaekel, Hubert Hackl, Andreas Wilfer, Clara Zoellig, Monika Haemmerle, Carsten Müller-Tidow, Haifa Kathrin Al-Ali, Barbara Seliger, Claudia Wickenhauser","doi":"10.1038/s41375-025-02706-3","DOIUrl":"10.1038/s41375-025-02706-3","url":null,"abstract":"Constitutive JAK/STAT pathway activation is crucial in the pathogenesis of BCR::ABL1-negative myeloproliferative neoplasms (MPN), but has not yet been linked to interferon (IFN)-γ signaling and tumor microenvironment. Human JAK2 V617F-mutated cell lines, 265 bone marrow biopsies (BMB) of two MPN cohorts, and 50 non-neoplastic BMB, revealed an intrinsic activation of IFN-γ signaling, which was confirmed by public RNA expression data. In vitro analysis of JAK2-mutated cell lines showed an activation of IFN-γ signaling pathway in the absence of IFN-γ in the cell supernatants. In addition, a heterogeneous, but increased expression of IFN-γ signaling components was found in BMB of JAK2-mutated samples with the highest expression in lymphocytes and monocytes, accompanied by increased tumor infiltrating lymphocytes (TIL). Unsupervised clustering identified a prognostic favorable cluster in both patient cohorts characterized by augmented IFN-γ signaling and TILs. This cluster was enriched with JAK2-mutated, JAK-inhibition naive MPN, mainly essential thrombocythemia and polycythemia vera with mild bone marrow fibrosis. Moreover, in silico data confirmed the link between JAK2 mutations and increased IFN-γ signaling. Multivariate Cox regression revealed TILs to be the strongest prognostic marker. In conclusion, JAK2-mutated MPN exhibit an intrinsic activation of IFN-γ signaling associated with changes in the BM TME and patients’ outcome.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2391-2405"},"PeriodicalIF":13.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02706-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Refining renal response assessment in monoclonal immunoglobulin deposition disease: Challenges, limitations and need for consensus 改进单克隆免疫球蛋白沉积病的肾反应评估:挑战、限制和需要达成共识
IF 13.4 1区 医学
Leukemia Pub Date : 2025-08-05 DOI: 10.1038/s41375-025-02686-4
Sabine Karam, Matthew J. Pianko, Hani Hassoun
{"title":"Refining renal response assessment in monoclonal immunoglobulin deposition disease: Challenges, limitations and need for consensus","authors":"Sabine Karam, Matthew J. Pianko, Hani Hassoun","doi":"10.1038/s41375-025-02686-4","DOIUrl":"10.1038/s41375-025-02686-4","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 9","pages":"2072-2075"},"PeriodicalIF":13.4,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02686-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778506","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Bidirectional anti-tumor and immunological strategies by targeting GARP–TGF-β axis in adult T-cell leukemia/lymphoma GARP-TGF-β轴在成人t细胞白血病/淋巴瘤中的双向抗肿瘤和免疫策略
IF 13.4 1区 医学
Leukemia Pub Date : 2025-08-04 DOI: 10.1038/s41375-025-02725-0
Kako Suzuki, Seina Kusayanagi, Yuta Kuze, Masato Hata, Shiho Kozuma, Koji Jimbo, Yasuhito Nannya, Yutaka Suzuki, Kaoru Uchimaru, Makoto Yamagishi
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