Leukemia最新文献

{"title":"Patterns of clonal hematopoiesis in aplastic anemia under immunosuppressive therapy.","authors":"Linzhu Tian, Lele Zhang, Ruonan Li, Wenyan Wang, Weiwang Li, Hong Pan, Zhen Gao, Jingyu Zhao, Yuechen Luo, Liwei Fang, Jun Shi","doi":"10.1038/s41375-026-03048-4","DOIUrl":"https://doi.org/10.1038/s41375-026-03048-4","url":null,"abstract":"<p><p>Aplastic anemia (AA) is an immune-mediated bone marrow failure disorder with 15-20% risk of clonal evolution. We analyzed 371 patients with AA receiving immunosuppressive therapy (IST). All patients underwent PNH testing and 357 evaluable for cytogenetic analysis. Two hundred and thirty-seven received serial targeted sequencing. Clonal characteristics were compared before and after IST across age, disease severity, and hematological response. Among the 237 patients, somatic mutations were detected in 53 patients (22%) at baseline and 97 (41%) after IST. Distinct patterns of mutational dynamics were observed under IST, with newly acquired mutations defined as Pattern 2 being most common. High-risk mutations such as ASXL1 expanded persistently, whereas favorable clones like BCOR and PIGA often contracted or remained stable. Older age was associated with heavier mutational burden, and disease severity was associated with greater increase in mutations. Cytogenetic abnormalities were observed in 18 of 357 patients (5%) and rose to 37 (10%) post-treatment. PNH clones were present in 20% of patients at baseline and remained relatively stable during follow-up, 15 patients progressed to PNH syndrome. Six patients evolved to myeloid neoplasms, including myelodysplastic syndromes and chronic myelomonocytic leukemia. These findings highlight the importance of long-term molecular surveillance (ClinicalTrials.gov number, NCT04645199).</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887785","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":"CD19-CAR T cells persist long-term in the cerebrospinal fluid of pediatric, adolescent and young adult patients with B-cell acute lymphoblastic leukemia.","authors":"Aimee C Talleur, Jean-Yves Métais, Ying Li, Sarah Schell, Polly Adams, Rebecca Epperly, Marleni Torres Nunez, Stephen Gottschalk, Swati Naik","doi":"10.1038/s41375-026-03108-9","DOIUrl":"https://doi.org/10.1038/s41375-026-03108-9","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887861","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":"Macrophage reprogramming, not CD8 T cell dynamics, characterizes durable disease control following PD-1 blockade in smoldering myeloma.","authors":"Noé Perron, Kane Foster, Tarek H Mouhieddine, Robert A Redd, Sophie Magidson, Jacqueline Perry, Ashlee Sturtevant, Christine Davie, Caroline Ricciardi, Frances Arters, Marjorie Marto, Amy Goguen, Yuxin Liu, Elizabeth K O'Donnell, Adam S Sperling, Jacob P Laubach, Paul G Richardson, Gad Getz, Romanos Sklavenitis-Pistofidis, Lorenzo Trippa, Yoshinobu Konishi, Omar Nadeem, Irene M Ghobrial","doi":"10.1038/s41375-026-03092-0","DOIUrl":"https://doi.org/10.1038/s41375-026-03092-0","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148887878","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":"KLF4/MLL3 complex axis drives NRBP2 transcription to eliminate acute myeloid leukemia cells.","authors":"Meng Yang, Ting Lu, Yicheng He, Cong Chen, Yifei Wang, Guohuan Sun, Yawei Zheng, Jiaxin Qin, Jiali Ye, Xiaowei Xie, Xiangnan Zhao, Honglin Duan, Biao Zhang, Yapu Li, Fang Dong, Chang Xu, Tao Cheng, Hui Cheng, Shangda Yang","doi":"10.1038/s41375-026-03117-8","DOIUrl":"https://doi.org/10.1038/s41375-026-03117-8","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is a heterogeneous malignancy rooted in hematopoietic stem cell dysregulation. Here, we identify the transcription factor Krüppel-like factor 4 (KLF4) as a potent suppressor of AML growth, with KLF4 overexpression markedly impairing AML cell proliferation. Mechanistically, KLF4 interacts with the lysine methyltransferase 2 C (MLL3/KMT2C) histone methyltransferase complex to activate transcription of nuclear receptor-binding protein 2 (NRBP2), a pseudokinase. Furthermore, integrated transcriptomic and functional analyses identify TNIK (TRAF2- and NCK-interacting kinase) as a pro-leukemic downstream effector restrained by the KLF4-NRBP2 axis. Pharmacological inhibition of TNIK with TNIK-IN-1 inhibits AML cell growth while exerting limited effects on normal hematopoietic cells. Together, these findings establish a KLF4/MLL3 complex-NRBP2 regulatory axis that restrains AML growth through suppression of TNIK expression and provide a rationale for further preclinical evaluation of TNIK inhibition as a therapeutic strategy in AML. Schematic model illustrating the mechanism by which the KLF4/MLL3 complex/NRBP2 axis regulates the progression of AML. In AML cells with basal KLF4 expression, higher expression of TNIK promotes the proliferation of AML cells (upper). Upon KLF4 overexpression, the TRD and ZnF domains of KLF4 bind to MLL3, which facilitates the recruitment of the MLL3 complex to the NRBP2 cis-regulatory regions. This activates NRBP2 transcription and subsequently downregulates TNIK expression, leading to the suppression of AML cell proliferation. Pharmacological inhibition of TNIK by TNIK-IN-1 reduces TNIK protein levels, represses AML cell growth, and induces cell apoptosis (lower). This study reveals a molecular mechanism by which KLF4 governs AML progression, providing a novel therapeutic target and a potential small-molecule inhibitor for AML treatment (Created in BioRender. he, Y. (2026) https://BioRender.com/q0q3j3q ).</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881070","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":"Jagged-dependent Notch signaling governs extracellular vesicle bioactivity in multiple myeloma.","authors":"Domenica Giannandrea, Valentina Citro, Natalia Platonova, Michela Colombo, Raffaella Adami, Lara Paonessa, Giulia Sauro, Silvia Ancona, Anna Pistocchi, Gilda Aiello, Alfonsina D'Amato, Elisabetta Calzavara, Francesca Guidotti, Gloria Sini, Mauro Turrini, Lavinia Casati, Elena Lesma, Raffaella Chiaramonte","doi":"10.1038/s41375-026-03121-y","DOIUrl":"https://doi.org/10.1038/s41375-026-03121-y","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880995","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":"Defining and predicting disease progression in myeloproliferative neoplasms: a proposed biomarker-driven approach.","authors":"Raajit K Rampal, Richard Winneker, Andrew Kuykendall, Laura C Michaelis, Ghaith Abu-Zeinah, Steffen Koschmieder, Jan Philipp Bewersdorf, Zi Yun Ng, Gabriella Hobbs, Bridget Marcellino, Linda Resar, Joseph Scandura, Anand Patel, John Mascarenhas, Aaron Gerds, Douglas Tremblay, Shane Mayack, Andriy Derkach, Florian H Heidel","doi":"10.1038/s41375-026-03103-0","DOIUrl":"https://doi.org/10.1038/s41375-026-03103-0","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874632","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":"Choice of hypomethylating agent for newly diagnosed TP53-mutant acute myeloid Leukemia: a COMMAND registry study.","authors":"Talha Badar, James Foran, Omer Jamy, Chenyu Lin, Anand Patel, Yu-Hung Wang, Mahesh Kumar, Rory M Shallis, Kendall Diebold, Alexander Coltoff, Aaron D Goldberg, Jan P Bewersdorf, Kenneth M Zabel, Charles Foucar, Yasmin Abaza, Guru S Murthy, Neil Palmisiano, Adam S DuVall, Vamsi Kota, Shyam A Patel, Amer M Zeidan, Hemant Murthy, Mohamed Kharfan-Dabaja, Ehab Atallah, Mark R Litzow","doi":"10.1038/s41375-026-03119-6","DOIUrl":"https://doi.org/10.1038/s41375-026-03119-6","url":null,"abstract":"<p><p>Although azacitidine (AZA) and decitabine (DEC) demonstrate comparable efficacy in AML, prior data suggest that DEC may induce deeper TP53 mutation clearance and higher response rates; however, direct comparisons in TP53-mutant (TP53-MT) AML are lacking. We conducted a large multicenter retrospective analysis to compare outcomes between DEC- and AZA-based induction, including combinations with venetoclax (VEN). Of 652 patients with newly diagnosed TP53-MT AML, 321 received HMA-based induction (DEC, n = 183; AZA, n = 138). Baseline clinical and genomic characteristics were comparable between the DEC and AZA groups. TP53 mutation subtype were not associated with outcomes, whereas multi-hit TP53 status was independently associated with inferior EFS and OS. In the propensity score-matched cohort, no significant differences in event-free survival (EFS; P = 0.920) or overall survival (OS; P = 0.927) were observed. Median EFS was 5.1, 3.4, 5.9, and 5.6 months, with 12-month estimates of 24%, 17%, 18%, and 16%, while median OS was 5.7, 7.1, 9.2, and 7.1 months, with corresponding 12-month OS rates of 31%, 23%, 29%, and 32% for DEC + VEN, AZA + VEN, DEC, and AZA, respectively. No significant pairwise differences were observed between regimens. These findings from a large multicenter cohort suggest that AZA- and DEC-based induction yield comparable survival outcomes in TP53-MT AML.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865553","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":"Association of sarcopenia with treatment tolerance in older adults with acute myeloid leukemia using artificial intelligence computed tomography-segmentation and a geriatric assessment.","authors":"Samuel J Yates, Elizabeth Terman, Lauren Miller, John F Cursio, Claire Wild, Megan Huisingh-Scheetz, Michael Zhang, Nicholas Feinberg, Karteek Popuri, Mirza Faisal Beg, Varun Akella, Hamed Youshanlouei, Afsheen Noorani, Jamie Mathews, Caner Saygin, Anand A Patel, Olatoyosi Odenike, Richard A Larson, Mariam T Nawas, Wendy Stock","doi":"10.1038/s41375-026-03099-7","DOIUrl":"https://doi.org/10.1038/s41375-026-03099-7","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865476","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":"Tisagenlecleucel for post-transplant relapse in young acute lymphoblastic leukemia patients: European real-world determinants of outcome.","authors":"Laura M Moser, Martin Hutter, Martina Ahlmann, Anna Alonso-Saladrigues, Andishe Attarbaschi, Francis A Ayuk, Claudia D Baldus, Adriana Balduzzi, Halvard Bonig, Jean-Pierre Bourquin, Jochen Buechner, Veit L Buecklein, Saskia Burridge, Friso G Calkoen, Gunnar Cario, Barbara De Moerloose, Gustavo de Oliveira Canedo, Marie-Emilie Dourthe, Tobias Feuchtinger, Anna Füreder, Julia Hauer, Marianne Ifversen, Andrea Jarisch, Krzysztof Kalwak, Jan-Henning Klusmann, Guido Kobbe, Christian Koenecke, Annette Künkele, Roland Meisel, Pietro Merli, Monika Mielcarek-Siedziuk, Fabian Müller, Ingo Müller, Sara Napolitano, Macarena Oporto Espuelas, Olaf Penack, Florence Rabian, Claudia Rossig, Martin G Sauer, Paul G Schlegel, Arend von Stackelberg, Brigitte Strahm, Semjon Willier, Peter Bader, Susana Rives, Nicolas Boissel, Franco Locatelli, Sara Ghorashian, André Baruchel","doi":"10.1038/s41375-026-03105-y","DOIUrl":"https://doi.org/10.1038/s41375-026-03105-y","url":null,"abstract":"<p><p>This multicenter real-world study identifies critical determinants of outcome for tisagenlecleucel (tisa-cel) in treating post-HSCT relapse in 220 children/young adults with B-ALL from 31 European centers. Median follow-up was 30.0 months, with a 43.6% 2-year event-free survival (EFS), 67.2% overall-survival (OS), and 57.1% incidence of CAR-T failure. CAR-T for relapse after transplant from a matched sibling donor (MSD) compared to alternative donors was associated with lower 2-year-OS (MSD 59.1%, mismatched donor MMD 80.2%, matched family/unrelated donor MFD/MUD 68.3%, p = 0.046). Two-year incidence of CAR-T failure was highest for MSD (MSD 73.8%, MFD/MUD 49.7%, MMD 52.2%, p = 0.006). Patients who had relapsed early (< 6 months post HSCT) showed inferior 2-year-EFS (23.7%) and OS (47.2%) compared to patients with late relapse, ≥ 6 months after HSCT (EFS 49.8%, p = 0.001; OS 73.9%, p < 0.001). Early relapse was associated with a higher incidence of CAR-T failure and relapse after tisa-cel, particularly CD19+ relapses. Outcomes correlated with disease burden at lymphodepletion: 2-year-OS was 81.7% for MRD-, 69.2% for MRD+, and 55.2% for patients in non-remission (p = 0.003), with incidence of CAR-T failure highest in non-remission. Prior transplant from an MSD, early post-HSCT relapse, and disease burden at lymphodepletion identify patients at increased risk of CAR-T failure after HSCT.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865545","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":"Incidence, prevalence, and survival outcomes of patients with myeloproliferative neoplasms in the United States: a Surveillance, Epidemiology, and End Results (SEER) database analysis, years 2000-2021.","authors":"Sachi Singhal, Rahul Mishra, Sankalp Arora, Noha Sharafeldin, Ruchi Desai, Tania Jain, Pankit Vachhani","doi":"10.1038/s41375-026-03124-9","DOIUrl":"10.1038/s41375-026-03124-9","url":null,"abstract":"<p><p>Myeloproliferative Neoplasms (MPNs) are rare hematologic neoplasms. The epidemiology and outcomes of these rare neoplasms warrant an update considering new diagnostic tools and advances in treatment options. NCI's Surveillance, Epidemiology and End Results (SEER)-17 registries were interrogated to analyze adult patients diagnosed with MPN [ICD-O-3 codes: polycythemia vera (PV) 9950/3, essential thrombocythemia (ET) 9962/3, primary myelofibrosis (PMF) 9961/3 and chronic myeloid leukemia (CML) 9875/3] during the years 2000 to 2021. Data of 63,242 (ET, n = 24,172; PV, n = 23,456; PMF, n = 6131; CML, n = 9483) patients were analyzed. The overall incidence rate (IR) for ET, PV, PMF and CML was 1.8, 1.7, 0.5 and 0.7 per 100,000 person-years, respectively. The incidence of ET, PV, and MF increased with age, and the majority of cases were seen after the age of 50. 5-year Relative Survival (RS) for PMF was 50.9% in 2009, to 57.4% in 2013 and 60.6% in 2016. The median overall survival (OS) was 152 months for ET, 150 months for PV, 48 months for PMF, and 202 months for CML. Advancing age was associated with adverse survival across MPN subtypes. Survival of patients with PMF continues to improve over recent years. Important racial and gender variations exist, which were noted in our study.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865482","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}