LeukemiaPub Date : 2025-05-27DOI: 10.1038/s41375-025-02647-x
Shi Feng, Ran Kong, Cong Wang, Qingbo Hao, Xiaoyu Xie, Haiyang Wang, Jingjing Han, Yu Zhang, Jan Elsner, Derek Mendy, Michael Haughey, Paul Krenitsky, Veronique Plantevin-Krenitsky, Patrick Papa, Frank Mercurio, Weilin Xie, Xiangxiang Zhou
{"title":"A highly selective and orally bioavailable casein kinase 1 alpha degrader through p53 signaling pathway targets B-cell lymphoma cells","authors":"Shi Feng, Ran Kong, Cong Wang, Qingbo Hao, Xiaoyu Xie, Haiyang Wang, Jingjing Han, Yu Zhang, Jan Elsner, Derek Mendy, Michael Haughey, Paul Krenitsky, Veronique Plantevin-Krenitsky, Patrick Papa, Frank Mercurio, Weilin Xie, Xiangxiang Zhou","doi":"10.1038/s41375-025-02647-x","DOIUrl":"https://doi.org/10.1038/s41375-025-02647-x","url":null,"abstract":"<p>The modest reduction in casein kinase 1 alpha (CK1α) by lenalidomide contributes to its clinical effectiveness in treating del(5q) myelodysplastic syndrome. However, the mechanism by which CK1α impacts lymphoma survival remains inadequately defined. We developed INNO-220, a CRBN-dependent CK1α degrader, by leveraging cytokine expression profiling in T cells. Unlike lenalidomide, INNO-220 is a highly selective and potent degrader of CK1α without affecting IKZF1/3. Screening across lymphoma cell lines revealed that cells harboring wild-type p53 and exhibiting constitutive NF-κB signaling were particularly sensitive to CK1α degradation yet resistant to Bruton tyrosine kinase inhibitors. Moreover, INNO-220 suppresses NF-κB signaling and activates p53 pathway, leading to complete inhibition of lymphoma tumor growth in vivo. Mechanistically, INNO-220 disrupts the assembly and function of the CARD11/BCL10/MALT1 complex, thereby inhibiting NF-κB signaling in stimulated T cells and lymphoma cells that harbor an activating mutation in CARD11. Moreover, we observed that activation of wild-type p53 upon INNO-220 treatment was sufficient to induce potent cancer cell death even in the absence of constitutive NF-κB activity. In summary, our findings introduce a selective CK1α degrader as a novel therapeutic approach for lymphoma, providing both mechanistic insights and a potential patient selection strategy in treating lymphoma and possibly other cancers.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"57 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144145584","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}
LeukemiaPub Date : 2025-05-26DOI: 10.1038/s41375-025-02653-z
Arwa Bohra, Rafla Hassan, Saurabh Zanwar, Dragan Jevremovic, Horatiu Olteanu, Wilson I. Gonsalves, Gregory Otteson, Pedro Horna, S. Vincent Rajkumar, Shaji Kumar
{"title":"Peripheral Blood Flow Cytometry-based Definition of Plasma Cell Leukemia","authors":"Arwa Bohra, Rafla Hassan, Saurabh Zanwar, Dragan Jevremovic, Horatiu Olteanu, Wilson I. Gonsalves, Gregory Otteson, Pedro Horna, S. Vincent Rajkumar, Shaji Kumar","doi":"10.1038/s41375-025-02653-z","DOIUrl":"https://doi.org/10.1038/s41375-025-02653-z","url":null,"abstract":"<p><b>TO THE EDITOR:</b></p><p>Plasma cell leukemia (PCL), an aggressive form of MM, is defined by the International Myeloma Working Group (IMWG) as the presence of ≥5% circulating plasma cells (CPCs) in the peripheral blood [1]. Moreover, PCL cases are frequently enriched in the translocation t(11;14), which presents with a lympho-plasmacytoid morphology, complicating detection through standard morphological examination [2].</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"33 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144137061","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}
LeukemiaPub Date : 2025-05-22DOI: 10.1038/s41375-025-02645-z
Vilma Dembitz, Sophie C. James, Paolo Gallipoli
{"title":"Targeting lipid metabolism in acute myeloid leukemia: biological insights and therapeutic opportunities","authors":"Vilma Dembitz, Sophie C. James, Paolo Gallipoli","doi":"10.1038/s41375-025-02645-z","DOIUrl":"https://doi.org/10.1038/s41375-025-02645-z","url":null,"abstract":"<p>Metabolic rewiring is a hallmark of malignant transformation in leukemic cells and the potential offered by its therapeutic targeting has garnered significant attention. The development of clinically relevant metabolic targeted therapies in acute myeloid leukemia (AML) has mostly focused on targeting mitochondrial energy production, but progress has been hampered by generalized toxicities. An alternative strategy is to shift the focus from targeting energy production to targeting more specialized metabolic functions, such as energy storage, the regulation of oxidative stress and availability of cofactors needed for the function of specific metabolic reactions. Lipid metabolism plays a role in many of these metabolic functions and its importance in AML maintenance and response to therapy is being increasingly recognized but needs to be adequately interpreted in the context of its interaction with the microenvironment, particularly the adipose niche. In this review, we provide an overview of our current understanding of AML cellular metabolic dependencies on fatty acid and lipid metabolism and discuss their relevance in the context of functional interactions with adipocytes. We highlight unresolved questions about how to best target lipid metabolism and suggest approaches needed to fully understand the interplay between malignant cells and their niche in the context of metabolic dependencies.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"57 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113901","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}
LeukemiaPub Date : 2025-05-22DOI: 10.1038/s41375-025-02549-y
Victoria Berg, Anna Lollies, Markus Schneider, Patricia Johansson, Marc A. Weniger, Emma Albertini, Fabio Facchetti, Stefano Ascani, Abubakar Moawia, Susanne Bens, Anja Fischer, Reiner Siebert, Wolfram Klapper, Luisa Lorenzi, Enrico Tiacci, Sylvia Hartmann, Bettina Budeus, Martin-Leo Hansmann, Ralf Küppers
{"title":"Common origin and somatic mutation patterns of composite lymphomas and leukemias","authors":"Victoria Berg, Anna Lollies, Markus Schneider, Patricia Johansson, Marc A. Weniger, Emma Albertini, Fabio Facchetti, Stefano Ascani, Abubakar Moawia, Susanne Bens, Anja Fischer, Reiner Siebert, Wolfram Klapper, Luisa Lorenzi, Enrico Tiacci, Sylvia Hartmann, Bettina Budeus, Martin-Leo Hansmann, Ralf Küppers","doi":"10.1038/s41375-025-02549-y","DOIUrl":"https://doi.org/10.1038/s41375-025-02549-y","url":null,"abstract":"<p>When two lymphomas occur concurrently or sequentially in a patient, it is a major question whether they derive from the same lymphocyte or hematopoietic precursor cell or developed independently. We studied four composite classic Hodgkin lymphomas (HL) and other mature B-cell lymphomas, and two composite mature B- and T-cell neoplasias by whole exome sequencing (WES). Analysis of their IGV genes revealed that three composite B-cell lymphomas originated from common germinal center-experienced B cells. WES identified shared somatic mutations in the lymphomas of these clonally related composite lymphomas, indicating their derivation from a common, pre-malignant precursor. Most mutations were restricted to one or the other of these lymphomas, likely explaining how distinct lymphomas developed from a common ancestral B cell. In the two B-cell/T-cell lymphoma cases, and a composite clonally unrelated HL/chronic lymphocytic leukemia, the lymphoma partners did not share any somatic mutations. In three cases, we identified potentially oncogenic variants also in cells serving as constitutional controls. These variants may have contributed to development of a composite lymphoma/leukemia. We provide additional evidence of frequent clonal relation in composite lymphomas, highlight the multistep transformation process of related lymphomas with a likely pre-malignant intermediate common precursor, and support the importance of constitutional variants in lymphomagenesis.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"136 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113899","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":"KK2845, a PBD dimer-containing antibody-drug conjugate targeting TIM-3-expressing AML","authors":"Jian Zou, Haruka Kinosada, Shin-ichiro Takayanagi, Toshihiko Ishii, Toru Amano, Kaito Nihira, Shohei Kanie, Maiko Adachi, Harunobu Tahara, Teppei Sakoda, Yoshikane Kikushige, Koichi Akashi, Hidetaka Satou","doi":"10.1038/s41375-025-02642-2","DOIUrl":"https://doi.org/10.1038/s41375-025-02642-2","url":null,"abstract":"<p>Acute myeloid leukemia (AML) is a common hematopoietic malignancy with high recurrence rates, and there is an urgent need for new therapeutic agents. T-cell immunoglobulin mucin-3 (TIM-3) is expressed on the surface of both LSCs and blasts in most AML patients, but not in normal hematopoietic stem cells (HSCs). We have developed KK2845, an antibody drug conjugate (ADC) that consists of an anti-TIM-3 fully human IgG1 antibody, a valine-alanine linker and a highly potent DNA cross-linking pyrrolobenzodiazepine (PBD) dimer SG3199. KK2845 exhibited potent cytotoxicity against AML cells both in vitro and in vivo. The cytotoxicity against AML cells was almost comparable between KK2845 and CD33-ADC, an anti-CD33 antibody conjugated with PBD dimer that has shown high remission rates in clinical studies. In addition to the cytotoxicity depending on PBD dimer, KK2845 also showed potent antibody-dependent cell cytotoxicity (ADCC) activity against AML cells. KK2845 showed less cytotoxicity against human normal bone marrow cells than CD33-ADC. The pharmacokinetics of KK2845 in cynomolgus monkey after intravenous infusion demonstrated a favorable profile. Taken together, these data suggest that KK2845 could be a novel ADC therapeutic in AML.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"32 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144113974","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}
LeukemiaPub Date : 2025-05-20DOI: 10.1038/s41375-025-02628-0
Gamze Tari Crochet, Selcen Ari-Yuka, Anja Fischer, Mohamed Chour, Alexis Claudel, Nouhoum Sako, Cyrielle Robe, Julie Naudet, Alexis Gonon, Diana Laure Mboumba, Nicolas Ortonne, Vincent Alcazer, Marie-Hélène Delfau-Larue, Reiner Siebert, Philippe Gaulard, François Lemonnier
{"title":"Induction of p53-mediated apoptosis by azacitidine in patient-derived xenograft follicular helper T-cell lymphoma model","authors":"Gamze Tari Crochet, Selcen Ari-Yuka, Anja Fischer, Mohamed Chour, Alexis Claudel, Nouhoum Sako, Cyrielle Robe, Julie Naudet, Alexis Gonon, Diana Laure Mboumba, Nicolas Ortonne, Vincent Alcazer, Marie-Hélène Delfau-Larue, Reiner Siebert, Philippe Gaulard, François Lemonnier","doi":"10.1038/s41375-025-02628-0","DOIUrl":"https://doi.org/10.1038/s41375-025-02628-0","url":null,"abstract":"<p>Follicular helper T-cell lymphoma (TFHL) is the most common non-cutaneous T-cell lymphoma in the Western world and is associated with a poor prognosis. Neoplastic cells rely heavily on the tumor microenvironment, demonstrated by the absence of TFHL-derived cell lines, which hinders therapeutic progress. To overcome this limitation, we developed and characterized patient-derived xenograft TFHL (TFHL-PDXs). Fifteen TFHLs were implanted into immunodeficient mice, generating nine PDXs. The tumor microenvironment was detected in the first passage but progressively disappeared in subsequent passages. <i>TET2</i> mutations persisted in all cases and TFHL-specific mutations were observed in most. The models were treated with azacitidine and patient sensitivity was fully recapitulated. To elucidate the mechanism of action of azacitidine, we analyzed the differences in DNA methylation and gene expression in six TFHL-PDX models. Global DNA hypomethylation occurred in azacitidine-treated cells in drug-sensitive models but not in the resistant ones. DNA hypomethylation was associated with global upregulation of gene expression, including that of various cancer-related pathways, suggestive of p53-pathway-mediated cytotoxicity. Overall, the PDXs recapitulated TFHL features and exhibited sensitivity to azacitidine. They also made it possible to decipher the mechanism responsible for the effect of azacitidine, revealing the activation of p53-mediated apoptosis associated with DNA hypomethylation.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"132 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097101","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}
LeukemiaPub Date : 2025-05-20DOI: 10.1038/s41375-025-02643-1
Xiaoyang Wang, Hang Yao, Jiaohao Chen, Xiaogu Liu
{"title":"Correspondence to “A novel lncRNA SNHG29 regulates EP300-related histone acetylation modification and inhibits FLT3-ITD AML development”","authors":"Xiaoyang Wang, Hang Yao, Jiaohao Chen, Xiaogu Liu","doi":"10.1038/s41375-025-02643-1","DOIUrl":"https://doi.org/10.1038/s41375-025-02643-1","url":null,"abstract":"<p>We read the article “A novel lncRNA SNHG29 regulates EP300-related histone acetylation modification and inhibits FLT3-ITD AML development” by Liu Shan et al. with great interest [1]. The study identified the role of the novel lncRNA SNHG29 in FLT3-ITD acute myeloid leukemia (AML), demonstrating that it suppresses AML progression by binding to and regulating the histone acetyltransferase EP300, thereby influencing histone acetylation modifications and the expression of key AML-related genes. The research team has provided new potential therapeutic targets and research directions for AML treatment, and their findings hold significant implications for developing novel therapeutic strategies against AML.</p><p>The article makes an important contribution to the field of AML research, but we note a number of issues that may affect reader understanding and the reproducibility of experimental results. First, in the results section titled “SNHG29 is associated with proliferation and drug sensitivity of FLT3-ITD AML cells”, the authors report that “Overexpressed SNHG29 significantly inhibited proliferation and colony formation of MV4-11 and MOLM-13 cells, manifested by CCK-8 and clone formation (Fig. 3C) results.” However, the colony-forming assay lacks critical experimental parameters that may affect the reproducibility of the experiments. We recommend that the authors provide essential methodological details (e.g., agar concentration, culture conditions, and colony-counting criteria [2, 3]) and include representative colony images for both the OV-NC and OV-SNHG29 groups to enhance the rigor of the data [4, 5].</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"11 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097169","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}
LeukemiaPub Date : 2025-05-20DOI: 10.1038/s41375-025-02626-2
Franziska Auer, Mina N. F. Morcos, Mikko Sipola, Irfan Akhtar, Sanni Moisio, Julia Vogt, Rebecca Haag, Mari Lahnalampi, Tiina J. Tuononen, Andrea Hanel, Anna Viitasalo, Ulrike A. Friedrich, Andreas Dahl, Carolin Prexler, Aleksandra A. Pandyra, Polina Stepensky, Masatoshi Takagi, Arndt Borkhardt, Merja Heinäniemi, Julia Hauer
{"title":"Trajectories from single-cells to PAX5-driven leukemia reveal PAX5-MYC interplay in vivo","authors":"Franziska Auer, Mina N. F. Morcos, Mikko Sipola, Irfan Akhtar, Sanni Moisio, Julia Vogt, Rebecca Haag, Mari Lahnalampi, Tiina J. Tuononen, Andrea Hanel, Anna Viitasalo, Ulrike A. Friedrich, Andreas Dahl, Carolin Prexler, Aleksandra A. Pandyra, Polina Stepensky, Masatoshi Takagi, Arndt Borkhardt, Merja Heinäniemi, Julia Hauer","doi":"10.1038/s41375-025-02626-2","DOIUrl":"https://doi.org/10.1038/s41375-025-02626-2","url":null,"abstract":"<p>PAX5 acts as a master regulator of B-cell proliferation and differentiation. Its germline and somatic deregulation have both been implicated in the development of B-cell precursor acute lymphoblastic leukemia (BCP-ALL). However, the process how reduced <i>PAX5</i> transcriptional activity mediates progression to BCP-ALL, is still poorly understood. Here, we characterized the longitudinal effects of PAX5 reduction on healthy, pre-leukemic and BCP-ALL cells at the single-cell level. Cell-surface marker analysis revealed a genotype-driven enrichment of the pre-BII population in healthy <i>Pax5</i><sup>±</sup> mice. This population showed downregulated B-cell receptor signaling, while DNA replication/repair and cell-cycle signaling pathways were upregulated. Moreover, we observed a shift in the kappa/lambda light chain ratio toward lambda rearranged B-cells. Transplantation experiments further validated a delay of <i>Pax5</i><sup>±</sup> pre-BII cells in maturation and transition to IgM-positivity. Additionally, single-cell RNA-Sequencing and bulk ATAC-Sequencing of different stages of BCP-ALL evolution showed that <i>Pax5</i><sup>±</sup> pre-leukemic cells lose their B-cell identity and display <i>Myc</i> activation. Subsequently, BCP-ALLs acquired additional RAG-mediated aberrations and driver mutations in JAK-STAT and RAS-signaling pathways. Together, this study elucidates molecular and functional checkpoints in PAX5-mediated pre-leukemic cell progression exploitable for therapeutic intervention and demonstrates that PAX5 reduction is sufficient to initiate clonal evolution to BCP-ALL through activation of MYC.</p><figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"18 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144097170","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}
LeukemiaPub Date : 2025-05-15DOI: 10.1038/s41375-025-02639-x
Michael W M Kühn,Naveen Pemmaraju,Florian H Heidel
{"title":"The evolving landscape of epigenetic target molecules and therapies in myeloid cancers: focus on acute myeloid leukemia and myeloproliferative neoplasms.","authors":"Michael W M Kühn,Naveen Pemmaraju,Florian H Heidel","doi":"10.1038/s41375-025-02639-x","DOIUrl":"https://doi.org/10.1038/s41375-025-02639-x","url":null,"abstract":"Research on myeloid neoplasms, a field that has been driving scientific advances in cancer for over 50 years, has yielded many discoveries that have fundamentally reshaped our understanding of cancer biology. These insights, often the product of leukemia research, have been instrumental in developing more mechanism-based treatments in the early 2000s [1]. Recognizing epigenetic dysregulation as a common disease mechanism in myeloid cancers has been groundbreaking regarding recent treatment developments that exploit chromatin-based oncogenic mechanisms. In the case of acute myeloid leukemia (AML), sequencing studies aimed at assessing the complement of genetic alterations demonstrated that more than 60% of AML cases harbored disease-driving mutations in epigenetic regulators. This high prevalence underscores the importance of epigenetic dysregulation in AML pathogenesis [2, 3]. Chromatin regulators commonly control disease-specific transcriptional programs, making them attractive therapeutic targets to manipulate neoplastic gene expression programs, particularly in myeloid neoplasms. Several drugs targeting epigenetic mechanisms and exploiting myeloid disease-specific dependencies have recently been approved for treating myeloid neoplasms. Many additional drugs are currently being investigated in clinical trials, and numerous new compound developments are being studied in preclinical studies. This manuscript will review (1) chromatin-based disease mechanisms, such as DNA methylation, chromatin regulatory complexes, and histone modifications, currently investigated for therapeutic exploitation in myeloid malignancies, and (2) therapeutic developments already approved or investigated for treating these diseases.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"15 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065833","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}
LeukemiaPub Date : 2025-05-13DOI: 10.1038/s41375-025-02641-3
Dennis A. Eichenauer, Aylin Basaran, Ina Bühnen, Michael Fuchs, Bastian von Tresckow, Andreas Rosenwald, Martin-Leo Hansmann, Heinz-Wolfram Bernd, Peter Borchmann, Wolfram Klapper, Sylvia Hartmann
{"title":"Refining histopathological growth pattern-based risk group discrimination in nodular lymphocyte-predominant Hodgkin lymphoma: an analysis from the German Hodgkin Study Group","authors":"Dennis A. Eichenauer, Aylin Basaran, Ina Bühnen, Michael Fuchs, Bastian von Tresckow, Andreas Rosenwald, Martin-Leo Hansmann, Heinz-Wolfram Bernd, Peter Borchmann, Wolfram Klapper, Sylvia Hartmann","doi":"10.1038/s41375-025-02641-3","DOIUrl":"https://doi.org/10.1038/s41375-025-02641-3","url":null,"abstract":"<p>Histopathological growth patterns (GP) in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) have previously been divided into GP AB (typical) vs CDEF (variant). However, it is unclear whether this division is optimal. We thus investigated alternative GP grouping approaches (GP ABC vs DEF; GP ABCF vs DE). Overall, 583 NLPHL patients who had first-line treatment within GHSG trials were included in the analysis. Median age was 39 years; 74% of patients were male; 76% presented with early-stage and 24% with advanced-stage disease. The 5-year and 10-year progression-free survival (PFS) estimates for all patients were 85.9% and 76.6%; overall survival (OS) estimates were 95.8% and 94.5%. Significant PFS and OS differences were detected for the comparison GP ABCF vs DE with worse outcomes for the GP DE group (HR: 1.7; 95%-CI: 1.1–2.7; HR: 2.5; 95%-CI: 1.1–5.7). No PFS and OS differences were observed for the comparisons GP AB vs CDEF and GP ABC vs DEF. Median time to death was shorter and death more often due to NLPHL in the GP DE (13 months; 66.7%) than in the GP ABCF (31 months; 5.6%) group. Hence, the division of GP into GP ABCF vs DE allows an optimized GP-based risk group discrimination in NLPHL.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"113 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143940625","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}
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