Leukemia最新文献

{"title":"Commentary on the 2022 WHO Classification of Haematolymphoid Tumours: Myeloid and histiocytic/dendritic neoplasms","authors":"Robert Peter Gale, Christophe Badie","doi":"10.1038/s41375-025-02544-3","DOIUrl":"10.1038/s41375-025-02544-3","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 4","pages":"1009-1010"},"PeriodicalIF":12.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143666010","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":"Outcomes of frailty subgroups of older adults (age ≥ 70) treated with teclistamab: an International Myeloma Foundation immunotherapy database real-world analysis","authors":"Hira Mian, Thomas G. Martin, Gregory R. Pond, Sireesha Asoori, Rakesh Popat, Efstathios Kastritis, Joaquin Martinez-Lopez, Nadine Abdallah, Saurabh Chhabra, Ricardo Parrondo, Sikander Ailawadhi, Meletios A. Dimopoulos, Kwee Yong, Brian GM. Durie, Saad Z. Usmani, Yi Lin, Carlyn Rose Tan","doi":"10.1038/s41375-025-02552-3","DOIUrl":"https://doi.org/10.1038/s41375-025-02552-3","url":null,"abstract":"<p>Teclistamab, BCMA bispecific antibody (BsAb), was approved based upon the MajesTEC-1 study [1] with an overall response rate (ORR) of 63% and a median progression-free survival (PFS) of 11.3 months. In MajesTEC-1, the median age was 64 years, and patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥ 2 were excluded, suggesting that the vast majority of patients were fit. This has lead to a paucity of data both in clinical trials as well as in the real-world regarding the outcomes of older adults treated with BsAbs. We performed a retrospective analysis to understand the outcomes of older adults (age ≥ 70) including frail patients treated in the real-world with teclistamab.</p><p>This is was an multicenter retrospective study of patients with relapsed and/or refractory MM enrolled in the International Myeloma Foundation (IMF) immunotherapy database and treated with teclistamab at 7 academic centers across 5 countries between May 2022-Dec 2023. This study received approval from the Institutional Review Boards of the respective participating institutions and inidivdual patients were consented in accordance. Frailty categorization was done using the simplified frailty index and patients categorized as fit (score 0-1) or frail (≥ score 2) [2].</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"93 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143666005","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":"Bcor loss promotes Richter transformation of chronic lymphocytic leukemia associated with Notch1 activation in mice","authors":"Chiara Rompietti, Francesco Maria Adamo, Daniele Sorcini, Filomena De Falco, Arianna Stella, Giovanni Martino, Barbara Bigerna, Erica Dorillo, Estevão Carlos Silva Barcelos, Angela Esposito, Clelia Geraci, Roberta Arcaleni, Jessica Bordini, Lydia Scarfò, Emanuela Rosati, Paolo Ghia, Brunangelo Falini, Paolo Sportoletti","doi":"10.1038/s41375-025-02557-y","DOIUrl":"https://doi.org/10.1038/s41375-025-02557-y","url":null,"abstract":"<p>Richter’s transformation (RT) is an aggressive lymphoma occurring upon progression from chronic lymphocytic leukemia (CLL). Despite advances in deciphering the RT genetic architecture, the mechanisms driving this disease remain unknown. BCOR disruptive mutations were found in CLL and frequently associated with <i>NOTCH1</i> aberrations, a common feature in CLL and RT. We engineered mice to knock-out Bcor in B and CLL cells of Eμ-<i>TCL1</i> mice. Bcor loss resulted in alterations of the B cell compartment and favored CLL transformation into an aggressive lymphoma with reduced survival in Eμ-<i>TCL1</i> mice. RNA-sequencing demonstrated a molecular signature reminiscent of human RT and implied the involvement of the T cell tumour microenvironment in the disease onset. Bcor deficiency was associated with Notch1 activation in splenic CD19 + CD5+ cells to accelerate Eμ<i>-TCL1</i> mice lymphoproliferation. Notch1 inhibition progressively reduced circulating CD19+ CD5+ and RT cells infiltrating the spleen of diseased mice with concomitant reduction of PD-1 expressing T cells and improved survival. Our data demonstrated an interplay between the tumour suppressor activity of Bcor and Notch1 in RT pathogenesis with potential for tumour targeting. This model represented a new platform to uncover promising alternatives for this incurable tumour.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"92 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143661354","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":"Three-year analysis of adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia treated with brexucabtagene autoleucel in ZUMA-3","authors":"Bijal D. Shah, Ryan D. Cassaday, Jae H. Park, Roch Houot, Aaron C. Logan, Nicolas Boissel, Thibaut Leguay, Michael R. Bishop, Max S. Topp, Kristen M. O’Dwyer, Dimitrios Tzachanis, Martha L. Arellano, Yi Lin, Maria R. Baer, Gary J. Schiller, Marion Subklewe, Mehrdad Abedi, Monique C. Minnema, William G. Wierda, Daniel J. DeAngelo, Patrick Stiff, Deepa Jeyakumar, Daqin Mao, Sabina Adhikary, Lang Zhou, Tsveta Hadjivassileva, Rita Damico Khalid, Armin Ghobadi, Olalekan O. Oluwole","doi":"10.1038/s41375-025-02532-7","DOIUrl":"https://doi.org/10.1038/s41375-025-02532-7","url":null,"abstract":"<p>Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 CAR T-cell therapy approved in the US to treat adults aged ≥18 years (≥26 years in the EU) with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL). Brexu-cel showed an overall complete remission (CR)/CR with incomplete hematologic recovery (CRi) rate of 73% (CR rate 60%) and median overall survival (OS) of 25.4 months in 78 patients with R/R B-ALL after 2 years in ZUMA-3. Here, we report updated outcomes after &gt;3 years median follow-up. As of July 23, 2022, median follow-up in all patients (<i>N </i>= 78) was 41.6 months. Median OS (95% CI) was 25.6 months (1.2-47.0; <i>N </i>= 78) and was 38.9 months (25.4–not estimable) for responders (<i>n </i>= 58), with 9 patients in ongoing remission without subsequent therapies. Five deaths (none deemed brexu-cel–related) occurred since prior data cut. Benefits from brexu-cel were maintained regardless of age, prior therapies, and subsequent allogeneic stem cell transplantation (alloSCT). Subsequent alloSCT was not associated with survival benefit among responders versus responders without subsequent alloSCT. No secondary T-cell malignancies were reported in ZUMA-3 with long-term follow-up.</p><figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"33 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143653531","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":"Establishment and molecular characterisation of patient-derived organoids for primary central nervous system lymphoma","authors":"Shengjie Li, Jun Ren, Jianing Wu, Zuguang Xia, Yingzhu Li, Chengxun Li, Wenjun Cao","doi":"10.1038/s41375-025-02562-1","DOIUrl":"https://doi.org/10.1038/s41375-025-02562-1","url":null,"abstract":"<p>Primary central nervous system lymphoma (PCNSL) exhibits substantial intratumoural and intertumoural heterogeneity, complicating the development of effective treatment methods. Existing in vitro models fail to simulate the cellular and mutational diversity of native tumours and require prolonged generation times. Therefore, we developed a culture method for patient-derived PCNSL organoids (CLOs) and evaluated the organoids through extensive molecular characterisation, histopathological analysis, single-nucleus RNA sequencing, bulk RNA sequencing and whole-exome sequencing. These CLOs accurately mimicked the histological attributes, gene expression landscapes and mutational profiles of their original tumours. Single-nucleus RNA sequencing also revealed that CLOs maintained cell-type heterogeneity and the molecular signatures of their original tumours. CLOs were generated within 2 weeks, demonstrating rapid development and reliability. Therapeutic profiling was performed on three selected CLOs treated with four standard drugs. The CLOs exhibited specific sensitivity to methotrexate, and resistance to dexamethasone, ibrutinib and rituximab, suggesting that CLOs may be valuable tools for reflecting drug sensitivities. Taken together, these results emphasise that CLOs effectively emulate the key characteristics of PCNSL, increasing the understanding of the genetic landscape of this complex disease. CLOs provide a rapid and reliable platform for exploring individualised treatment strategies, potentially accelerating the transition of research findings to clinical practice.</p><figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"11 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640646","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":"The proto-oncogenic miR-106a-363 cluster enhances adverse risk acute myeloid leukemia through mitochondrial activation","authors":"Nadine Sperb, Irina A. Maksakova, Leo Escano, Libin Abraham, Liam MacPhee, Ariene Cabantog, Dexter Kim, Mansen Yu, Kathrin Krowiorz, Junbum Im, Sarah Grasedieck, Nicole Pochert, Christoph Ruess, Reinhild Rösler, Stephane Flibotte, Tobias Maetzig, Enrico Calzia, Lars Palmqvist, Sebastian Wiese, Linda Fogelstrand, Michael R. Gold, Arefeh Rouhi, Florian Kuchenbauer","doi":"10.1038/s41375-025-02558-x","DOIUrl":"https://doi.org/10.1038/s41375-025-02558-x","url":null,"abstract":"<p>We investigated the clinical and functional role of the miR-106a-363 cluster in adult acute myeloid leukemia (AML). LAML miRNA-Seq TCGA analyses revealed that high expression of miR-106a-363 cluster members was associated with inferior survival, and miR-106a-5p and miR-20b-5p levels were significantly elevated in patients with adverse risk AML. Overexpression of the miR-106a-363 cluster and its individual members in a murine AML model significantly accelerated leukemogenesis. Proteomics analysis of leukemic bone marrow cells from these models emphasized the deregulation of proteins involved in intracellular transport, protein complex organization and mitochondrial function, driven predominantly by miR-106a-5p. These molecular alterations suggested mitochondrial activation as a potential mechanism for the observed increase in leukemogenicity. High-resolution respirometry and STED microscopy confirmed that miR-106a-5p enhances mitochondrial respiratory activity and increases mitochondrial volume. These findings demonstrate that the miR-106a-363 cluster, and particularly miR-106a-5p, contribute to AML progression through modulation of mitochondrial function and deregulation of mitochondria-coordinated pathways.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"2 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640648","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":"KDM4B modulates autocrine IL6 in erythroblasts to prevent ineffective erythropoiesis","authors":"Zheng Peng, Dan Su, Jing-jing Xu, Lin-hang Zhou, Zu-qiang Fu, Liu Yang, Wen-xin Wang, Ai-hua Gu, Yong Zhou","doi":"10.1038/s41375-025-02559-w","DOIUrl":"https://doi.org/10.1038/s41375-025-02559-w","url":null,"abstract":"<p>Ineffective erythropoiesis (IE) commonly underlies anemia in congenital disorders. However, the causes of IE remain largely unknown. Recently, attention has been drawn to the involvement of nucleated erythrocytes in immune responses, providing a new perspective for exploring the etiology of IE. In this study, we found that the <i>kdm4b</i>⁻^/⁻ mutant zebrafish developed an IE-like defect, including impaired terminal maturation and apoptosis of erythroblasts, as confirmed by observations in <i>Kdm4b</i>⁻^/⁻ mutant mice. Thus, the <i>Kdm4b</i> mutant serves as an appropriate model for studying IE. Mechanistically, <i>kdm4b</i> primarily targets interleukin 6 (<i>il6</i>) to regulate the previously underrated immune activity of embryonic erythroblasts. The erythroblast-secreted Il6, in the absence of <i>kdm4b</i>, increased pro-inflammatory activities of myeloid cells and elevated T cell counts. Meanwhile, the activated Il6-pStat3 signaling elevated mitochondrial oxidative stress, leading to the maturation arrest of erythroblasts. Collectively, we demonstrate an important role for <i>kdm4b</i> in coordinating terminal maturation and immune function in erythroblasts. These findings might shed light on our understanding of the etiology of IE and the discovery of new effective compounds.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"105 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608475","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":"Impact of treatment for adolescent and young adults with essential thrombocythemia and polycythemia vera","authors":"Yan Beauverd, Jean-Christophe Ianotto, Kyaw Htin Thaw, Marta Sobas, Parvis Sadjadian, Natalia Curto-Garcia, Lee-Yung Shih, Timothy Devos, Dorota Krochmalczyk, Serena Galli, Maria Bieniaszewska, Ilona Seferynska, Mary Frances McMullin, Anna Armatys, Adrianna Spalek, Joanna Waclaw, Mihnea Tudor Zdrenghea, Laurence Legros, Francois Girodon, Krzysztof Lewandowski, Beatriz Bellosillo, Jan Samuelsson, Aitor Abuin Blanco, Pascale Cony-Makhoul, Angela Collins, Chloe James, Rajko Kusec, Marie Lauermannova, Maria Soledad Noya, Malgorzata Skowronek, Lukasz Szukalski, Anna Szmigielska-Kaplon, Marielle Wondergem, Iryna Dudchenko, Joanna Gora-Tybor, Kamel Laribi, Anna Kulikowska de Nałęcz, Jean-Loup Demory, Katell Le Dû, Sonja Zweegman, Carlos Besses Raebel, Radek C. Skoda, Stephane Giraudier, Martin Griesshammer, Jean-Jacques Kiladjian, Claire N Harrison","doi":"10.1038/s41375-025-02545-2","DOIUrl":"https://doi.org/10.1038/s41375-025-02545-2","url":null,"abstract":"<p>Essential thrombocythemia (ET) and polycythemia vera (PV) are rare in adolescent and young adult (AYA). These conditions, similar to those in older patients, are linked with thrombotic complications and the potential progression to secondary myelofibrosis (sMF). This retrospective study of ET and PV patients diagnosed before age 25 evaluated complication rates and impact of cytoreductive drugs on outcomes. Among 348 patients (278 ET, 70 PV) with a median age of 20 years, the of thrombotic events was 1.9 per 100 patient-years. Risk factors for thrombosis included elevated white blood cell count (&gt;11 × 10⁹/L) (HR: 2.7, <i>p</i> = 0.012) and absence of splenomegaly at diagnosis (HR: 5.7, <i>p</i> = 0.026), while cytoreductive drugs did not reduce this risk. The incidence of sMF was 0.7 per 100 patient-years. <i>CALR</i> mutation (HR: 6.0, <i>p</i> &lt; 0.001) and a history of thrombosis (HR: 3.8, <i>p</i> = 0.015) were associated with sMF risk. Interferon as a first-line treatment significantly improved myelofibrosis-free survival compared to other treatments or the absence of cytoreduction (<i>p</i> = 0.046). Although cytoreduction did not affect thrombotic event, early interferon use reduced sMF risk. These findings support interferon use to mitigate sMF risk in AYA ET and PV patients.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"22 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608476","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":"Intensive post-remission therapy does not decrease relapse after allotransplants for acute myeloid leukaemia in 1st remission and should not be given","authors":"E. Rodríguez-Arbolí, G. L. Phillips, T. S. Pardee, H. M. Lazarus, R. P. Gale","doi":"10.1038/s41375-025-02560-3","DOIUrl":"https://doi.org/10.1038/s41375-025-02560-3","url":null,"abstract":"<blockquote><p><i>The truth will set you free but first it will make you miserable</i>.</p>\u0000<p>President James A. Garfield</p></blockquote><p><i>The truth will set you free but first it will make you miserable</i>.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"87 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608474","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":"Comparison of subcutaneous injection versus intravenous infusion of cytarabine for induction therapy in adult acute myeloid leukemia","authors":"Huafeng Wang,&nbsp;Shanshan Suo,&nbsp;Dengju Li,&nbsp;Jianyong Li,&nbsp;Lu Liu,&nbsp;Ying Lu,&nbsp;Jianping Shen,&nbsp;Chunyan Ji,&nbsp;Tong Chen,&nbsp;Kang Yu,&nbsp;Hanyun Ren,&nbsp;Yan Li,&nbsp;Ying Chen,&nbsp;Shaolei Zang,&nbsp;Bin Liang,&nbsp;Sijing Kang,&nbsp;Jinghan Wang,&nbsp;Wei Cheng,&nbsp;Wenjuan Yu,&nbsp;Haitao Meng,&nbsp;Hongyan Tong,&nbsp;Jie Jin","doi":"10.1038/s41375-025-02556-z","DOIUrl":"10.1038/s41375-025-02556-z","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 4","pages":"976-979"},"PeriodicalIF":12.8,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143608071","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}