Leukemia最新文献

筛选
英文 中文
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
{"title":"Bidirectional anti-tumor and immunological strategies by targeting GARP–TGF-β axis in adult T-cell leukemia/lymphoma","authors":"Kako Suzuki, Seina Kusayanagi, Yuta Kuze, Masato Hata, Shiho Kozuma, Koji Jimbo, Yasuhito Nannya, Yutaka Suzuki, Kaoru Uchimaru, Makoto Yamagishi","doi":"10.1038/s41375-025-02725-0","DOIUrl":"10.1038/s41375-025-02725-0","url":null,"abstract":"In adult T-cell leukemia/lymphoma (ATL), tumor cells show a regulatory T-cell (Treg)-type phenotype, which influences their tumor immunity. However, our knowledge of what molecular events are involved in pathogenesis is still missing. Here, we took advantage of this unique phenotype and screened whole transcriptome data from primary ATL cells to search for effective therapeutic targets. Glycoprotein A repetitions predominant (GARP) was identified as a novel tumor antigen in ATL. ATL cells overexpress GARP and release transforming growth factor-β (TGF-β). The GARP–TGF-β axis promotes cell proliferation of ATL cells and human T-cell leukemia virus type 1 (HTLV-1)-infected cells with changes in cell signaling activities and shaping of Treg gene expression patterns, but suppresses the activity of surrounding effector T-cells. Remarkably, this study has provided a breakthrough therapeutic concept that achieves the dual effect of direct tumor cell depletion and indirect immune activation by a single treatment targeting GARP. DS-1055a, an anti-GARP monoclonal antibody, selectively and effectively depleted malignant ATL cells via antibody-dependent cellular cytotoxicity, supporting the proof-of-concept in the preclinical study. Our findings highlight the key to understanding the cell origin of ATL and developing unprecedented therapeutic strategies for refractory diseases.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2465-2476"},"PeriodicalIF":13.4,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02725-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778087","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
Author’s Reply to the correspondence: ECIL-10 guidelines for COVID-19 should take convalescent plasma into proper consideration by Focosi et al. 作者回复:ECIL-10 COVID-19指南应适当考虑Focosi等人的恢复期血浆。
IF 13.4 1区 医学
Leukemia Pub Date : 2025-08-04 DOI: 10.1038/s41375-025-02721-4
Simone Cesaro, Per Ljungman, Malgorzata Mikulska, Hans H. Hirsch, David Navarro, Catherine Cordonnier, Varun Mehra, Jan Styczynski, Francesco Marchesi, Jose Luis Pinana, Gernot Beutel, Herman Einsele, Johan Maertens, ECIL-10, Rafael de la Camara
{"title":"Author’s Reply to the correspondence: ECIL-10 guidelines for COVID-19 should take convalescent plasma into proper consideration by Focosi et al.","authors":"Simone Cesaro, Per Ljungman, Malgorzata Mikulska, Hans H. Hirsch, David Navarro, Catherine Cordonnier, Varun Mehra, Jan Styczynski, Francesco Marchesi, Jose Luis Pinana, Gernot Beutel, Herman Einsele, Johan Maertens, ECIL-10, Rafael de la Camara","doi":"10.1038/s41375-025-02721-4","DOIUrl":"10.1038/s41375-025-02721-4","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 9","pages":"2304-2305"},"PeriodicalIF":13.4,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144778086","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 bone marrow immune ecosystem shapes daratumumab acquired resistance in plasma cell myeloma 骨髓免疫生态系统在浆细胞骨髓瘤中形成达拉单抗获得性耐药
IF 13.4 1区 医学
Leukemia Pub Date : 2025-08-01 DOI: 10.1038/s41375-025-02712-5
Yun Wang, Shuzhao Chen, Zhijian Liang, Robert Peter Gale, Shutong Liu, Xiaoqin Chen, Peidong Chi, Yiling Song, Yingchun Zhang, Weida Wang, Juan Li, Zhongjun Xia, Yang Liang, Xiaojun Huang
{"title":"The bone marrow immune ecosystem shapes daratumumab acquired resistance in plasma cell myeloma","authors":"Yun Wang, Shuzhao Chen, Zhijian Liang, Robert Peter Gale, Shutong Liu, Xiaoqin Chen, Peidong Chi, Yiling Song, Yingchun Zhang, Weida Wang, Juan Li, Zhongjun Xia, Yang Liang, Xiaojun Huang","doi":"10.1038/s41375-025-02712-5","DOIUrl":"10.1038/s41375-025-02712-5","url":null,"abstract":"Daratumumab, an anti-CD38 monoclonal antibody, is an effective therapy for plasma cell myeloma (PCM). However, many initial responders relapse. We compared paired samples from subjects pre-therapy and then acquired resistance to daratumumab. We first used single-cell RNA sequencing and digital spatial profiler (DSP). The proportion of cytotoxic CD8-positive T-cells with an exhaustion phenotype and an IFN-γ signature increased in resistance compared with pre-therapy samples, whilst the proportion of NK-cells decreased and had an increased inhibitory phenotype. Transcription of CD38 in neoplastic plasma cells decreased. Numbers of immune cells in cancer centre defined by DSP were significantly decreased in parallel with an increased exhaustion signature. The acquired resistance signature and elevated PCM subset phenotype were associated with worse prognosis in 4 external cohorts (GSE24080, GSE136337, GSE57317, and coMMpass). Using single-cell regulatory network inference, we identified MYC regulation as a key activated factor for acquired resistance in neoplastic plasma cells by intersecting the top 20 upregulated regulons and upregulated genes in acquired resistance. Furthermore, data from in vitro and in vivo experiments indicate that IFN-γ secreted by cells of bone marrow immune ecosystem activates MYC, which correlates with acquired daratumumab resistance. Our data provide insights into acquired daratumumab resistance and suggest potential therapeutic strategies.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2504-2515"},"PeriodicalIF":13.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02712-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756375","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
Evaluating a predictive model of tyrosine kinase inhibitor therapy failure in a European-type cohort: a step towards population-specific tools 评估欧洲型队列中酪氨酸激酶抑制剂治疗失败的预测模型:迈向人群特异性工具的一步
IF 13.4 1区 医学
Leukemia Pub Date : 2025-08-01 DOI: 10.1038/s41375-025-02703-6
Sylvain Moinard, Benjamin Lebecque, Tom Lachaise, Hyacinthe Johnson-Ansah, Charlotte Doublet, Gabrielle Roth-Guepin, Françoise Rigal-Huguet, Lydia Roy, Anne Parry, Mathieu Meunier, Amélie Penot, Laurence Legros, Vanessa Pante, Martine Escoffre-Barbe, Philippe Rousselot, Guillaume Denis, Hélène Monjanel, Dalil Hamroun, Abdessattar Khlaifia, Joévin Besombes, Bruno Pereira, Céline Bourgne, Marc G. Berger
{"title":"Evaluating a predictive model of tyrosine kinase inhibitor therapy failure in a European-type cohort: a step towards population-specific tools","authors":"Sylvain Moinard, Benjamin Lebecque, Tom Lachaise, Hyacinthe Johnson-Ansah, Charlotte Doublet, Gabrielle Roth-Guepin, Françoise Rigal-Huguet, Lydia Roy, Anne Parry, Mathieu Meunier, Amélie Penot, Laurence Legros, Vanessa Pante, Martine Escoffre-Barbe, Philippe Rousselot, Guillaume Denis, Hélène Monjanel, Dalil Hamroun, Abdessattar Khlaifia, Joévin Besombes, Bruno Pereira, Céline Bourgne, Marc G. Berger","doi":"10.1038/s41375-025-02703-6","DOIUrl":"10.1038/s41375-025-02703-6","url":null,"abstract":"Predicting therapeutic failure in patients with chronic phase-chronic myeloid leukemia (CP-CML) treated with tyrosine kinase inhibitors (TKI) remains a major challenge for personalized care management. The Sokal and EUTOS long-term survival scores were designed to predict CML-related mortality, but are also used to guide therapeutic choices, despite their poor performance for this purpose. A recent study proposed a refined predictive model of therapy failure specifically tailored for patients treated with imatinib and second-generation TKIs that showed promising results in a Chinese cohort. The present study evaluated the performance and applicability of this predictive model in a real-world, multicenter cohort from the French CML Observatory. The key differences identified between the Chinese and French cohorts (age, baseline hemoglobin levels, and treatment regimens) likely influenced the model performance. Specifically, the new model did not allow for discriminating risk groups effectively in the French cohort. However, the model reconstruction using this cohort identified other predictive variables (sex, leukocytosis, comorbidities, high-risk additional chromosomal abnormalities) that better stratified patients at risk of therapy failure. Our findings highlight the influence of demographic and clinical differences on predictive models and emphasize the need for local or population-specific tools to optimize risk stratification and therapeutic decision-making in CP-CML.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2375-2383"},"PeriodicalIF":13.4,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02703-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756450","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
Combining MCL-1 inhibition and CD37-directed chimeric antigen receptor T cells as an effective strategy to target T-cell lymphoma MCL-1抑制与cd37靶向嵌合抗原受体T细胞联合作为靶向T细胞淋巴瘤的有效策略
IF 13.4 1区 医学
Leukemia Pub Date : 2025-07-30 DOI: 10.1038/s41375-025-02697-1
Tayla B. Heavican-Foral, Felix Korell, Irene Scarfò, Caroline R. M. Wiggers, Allen Thayakumar B, Zachary Eisenbies, Foster Powers, Justin Hegel, Jianlin Liu, Steffen Kulp, Harrison Silva, Gongwei Wu, Anthony Letai, Kimberly Stegmaier, Jens G. Lohr, David M. Weinstock, Marcela V. Maus, Birgit Knoechel
{"title":"Combining MCL-1 inhibition and CD37-directed chimeric antigen receptor T cells as an effective strategy to target T-cell lymphoma","authors":"Tayla B. Heavican-Foral, Felix Korell, Irene Scarfò, Caroline R. M. Wiggers, Allen Thayakumar B, Zachary Eisenbies, Foster Powers, Justin Hegel, Jianlin Liu, Steffen Kulp, Harrison Silva, Gongwei Wu, Anthony Letai, Kimberly Stegmaier, Jens G. Lohr, David M. Weinstock, Marcela V. Maus, Birgit Knoechel","doi":"10.1038/s41375-025-02697-1","DOIUrl":"10.1038/s41375-025-02697-1","url":null,"abstract":"Chimeric antigen receptor (CAR) T cell therapy has not yet been realized for T-cell lymphomas (TCL), partially due to challenges in identifying tumor-specific antigens. We previously reported selective expression of CD37 on malignant T cells in a subset of TCL. Herein, we demonstrate CAR-37 T cells specifically target CD37-positive TCL in part by activating the intrinsic apoptotic pathway. To maximize therapeutic index, we identified selective/targetable BH3 dependences in individual TCL models and combined with CAR-37 T cells. We show that BH3 mimetics do not alter CD37 antigen binding capacity on TCL and have minimal effects on CAR-37 T-cell phenotype or function. In TCL models with dependence on MCL-1, combining CAR-37 T cells and the MCL-1 inhibitor AZD5991 increases anti-TCL response and prolongs survival of xenografted mice. These findings suggest that personalized selection of BH3 mimetic/CAR-T combinations could maximize the therapeutic index for patients with TCL and possibly other diseases.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2452-2464"},"PeriodicalIF":13.4,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02697-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144737177","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
Liquid-liquid phase separation of ZHX2 protects DLBCL cells against ferroptosis through induction of SLC3A2 液-液相分离的ZHX2通过诱导SLC3A2对DLBCL细胞有保护作用
IF 13.4 1区 医学
Leukemia Pub Date : 2025-07-29 DOI: 10.1038/s41375-025-02718-z
Juan Zhang, Dongmei Wang, Mengfan Luan, Xiaomin Liu, Nana Wang, Xue Sheng, Shuying Li, Boya Li, Tao Sun, Daoxin Ma, Jingjing Ye, Fei Lu, Chunyan Ji
{"title":"Liquid-liquid phase separation of ZHX2 protects DLBCL cells against ferroptosis through induction of SLC3A2","authors":"Juan Zhang, Dongmei Wang, Mengfan Luan, Xiaomin Liu, Nana Wang, Xue Sheng, Shuying Li, Boya Li, Tao Sun, Daoxin Ma, Jingjing Ye, Fei Lu, Chunyan Ji","doi":"10.1038/s41375-025-02718-z","DOIUrl":"10.1038/s41375-025-02718-z","url":null,"abstract":"Diffuse large B-cell lymphoma (DLBCL), the most common B-cell non-Hodgkin lymphoma (B-NHL), is characterized by strong aggression, high heterogeneity, and poor prognosis. Consequently, there is an urgent need to identify crucial therapeutic targets. Here, we found that the transcription factor zinc-finger and homeobox 2 (ZHX2) was highly expressed in DLBCL. Subsequently, ZHX2 was proven to be critical for promoting DLBCL cell proliferation by inhibiting ferroptosis. Mechanistically, ZHX2 bound to the promoter region of the solute carrier family 3-member 2 (SLC3A2) gene through liquid-liquid phase separation (LLPS) and activated its function to negatively regulate ferroptosis. Furthermore, we constructed lipid nanoparticles ZHX2-siRNA@LNP targeting DLBCL, which effectively inhibited the growth of the tumors in vivo. In summary, our study indicated that the LLPS of ZHX2 protected DLBCL against ferroptosis through induction of SLC3A2, and disturbing it with ZHX2-siRNA@LNP could significantly repress DLBCL, providing a promising therapeutic strategy for DLBCL.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2442-2451"},"PeriodicalIF":13.4,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02718-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736787","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
Rare germline variant in NFATC4 associated with familial CLL 与家族性CLL相关的NFATC4罕见种系变异
IF 13.4 1区 医学
Leukemia Pub Date : 2025-07-28 DOI: 10.1038/s41375-025-02713-4
Gilad Itchaki, Harrison Bai, Grace Tiao, Reina Improgo, Ben E. Oppenheimer, Siddha Kasar, Bethany Tesar, Stacey M. Fernandes, Nathalie Pochet, John-Hanson Machado, Emily M. Thrash, Arnold S. Freedman, Gad Getz, Jennifer R. Brown
{"title":"Rare germline variant in NFATC4 associated with familial CLL","authors":"Gilad Itchaki, Harrison Bai, Grace Tiao, Reina Improgo, Ben E. Oppenheimer, Siddha Kasar, Bethany Tesar, Stacey M. Fernandes, Nathalie Pochet, John-Hanson Machado, Emily M. Thrash, Arnold S. Freedman, Gad Getz, Jennifer R. Brown","doi":"10.1038/s41375-025-02713-4","DOIUrl":"10.1038/s41375-025-02713-4","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 10","pages":"2547-2550"},"PeriodicalIF":13.4,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715613","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
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信