LeukemiaPub Date : 2025-07-17DOI: 10.1038/s41375-025-02693-5
Danielle R. Bond, Sean M. Burnard, Kumar Uddipto, Kooper V. Hunt, Brooke M. Harvey, Luiza Steffens Reinhardt, Charley Lawlor-O’Neill, Ellise A. Roper, Sam Humphries, Heather C. Murray, Abdul Mannan, Matthew D. Dun, Charles E. de Bock, Nikola A. Bowden, Anoop K. Enjeti, Nicole M. Verrills, Carlos Riveros, Kim-Anh Lê Cao, Heather J. Lee
{"title":"Hypomethylating agents induce epigenetic and transcriptional heterogeneity with implications for acute myeloid leukemia cell self-renewal","authors":"Danielle R. Bond, Sean M. Burnard, Kumar Uddipto, Kooper V. Hunt, Brooke M. Harvey, Luiza Steffens Reinhardt, Charley Lawlor-O’Neill, Ellise A. Roper, Sam Humphries, Heather C. Murray, Abdul Mannan, Matthew D. Dun, Charles E. de Bock, Nikola A. Bowden, Anoop K. Enjeti, Nicole M. Verrills, Carlos Riveros, Kim-Anh Lê Cao, Heather J. Lee","doi":"10.1038/s41375-025-02693-5","DOIUrl":"10.1038/s41375-025-02693-5","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 9","pages":"2275-2280"},"PeriodicalIF":13.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02693-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652197","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}
LeukemiaPub Date : 2025-07-16DOI: 10.1038/s41375-025-02707-2
Jennifer H. Cooperrider, Diren Arda Karaoglu, Tadeusz Kubicki, Can Rui Jiang, Ella Postich, Kathryn Shimamoto, Olivia Arnold, Jommel Macaraeg, Aubrianna Ramsland, Anna Pula, Ashwin Kishtagari, Yash Pershad, Taralynn M. Mack, Angela Jones, Alexander G. Bick, Michael Savona, Michael W. Drazer, Dominik Dytfeld, Andrzej Jakubowiak, Benjamin A. Derman, Caner Saygin
{"title":"Evolution of clonal hematopoiesis on and off lenalidomide maintenance for multiple myeloma","authors":"Jennifer H. Cooperrider, Diren Arda Karaoglu, Tadeusz Kubicki, Can Rui Jiang, Ella Postich, Kathryn Shimamoto, Olivia Arnold, Jommel Macaraeg, Aubrianna Ramsland, Anna Pula, Ashwin Kishtagari, Yash Pershad, Taralynn M. Mack, Angela Jones, Alexander G. Bick, Michael Savona, Michael W. Drazer, Dominik Dytfeld, Andrzej Jakubowiak, Benjamin A. Derman, Caner Saygin","doi":"10.1038/s41375-025-02707-2","DOIUrl":"10.1038/s41375-025-02707-2","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 9","pages":"2285-2288"},"PeriodicalIF":13.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02707-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640347","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}
LeukemiaPub Date : 2025-07-16DOI: 10.1038/s41375-025-02679-3
Tobias Rausch, Hendrik Schäfer, Julia Bein, Felix Mölder, Lilian Kara Beeck, Bernd Kölsch, Sabrina Borchert, Vladimir Benes, Teresa Halbsguth, Uta Brunnberg, Thomas Oellerich, Thomas Tousseyn, Maurilio Ponzoni, Johannes Köster, Martin-Leo Hansmann, Ralf Küppers, Sylvia Hartmann
{"title":"Genetic lesions in nodular lymphocyte-predominant Hodgkin lymphoma and T cell/histiocyte-rich large B-cell lymphoma identified by whole genome sequencing","authors":"Tobias Rausch, Hendrik Schäfer, Julia Bein, Felix Mölder, Lilian Kara Beeck, Bernd Kölsch, Sabrina Borchert, Vladimir Benes, Teresa Halbsguth, Uta Brunnberg, Thomas Oellerich, Thomas Tousseyn, Maurilio Ponzoni, Johannes Köster, Martin-Leo Hansmann, Ralf Küppers, Sylvia Hartmann","doi":"10.1038/s41375-025-02679-3","DOIUrl":"10.1038/s41375-025-02679-3","url":null,"abstract":"Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare malignant lymphoma characterised by a few large tumour cells expressing B-cell antigens in an inflammatory background. T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is now considered to be closely related to NLPHL. Little is known about the mutational spectrum of the lymphoma cells in primary NLPHL and THRLBCL due to the rarity of the diseases and the technical challenges of analysing these tumours. Therefore, the aim of the present study was to elucidate mechanisms contributing to the pathogenesis of NLPHL and THRLBCL by whole genome sequencing of laser microdissected tumour cells from seven cases. We observed a heterogeneity of transforming events, with cases showing abundant somatic mutations, others with a predominance of structural variations, and cases with few aberrations. The genes that were most frequently affected by aberrations encode factors influencing JAK-STAT, NF-κB, and/or WNT signaling, and apoptosis regulators. However, the mutated genes, such as SOCS3, JUNB, IRF1 and ITPKB, were not the typical targets known from classical Hodgkin lymphoma (cHL). Two cases showed recurrent rearrangements of BCL6 and CD74. In conclusion, our data enrich our understanding of NLPHL and THRLBCL and highlight common and distinct features with respect to cHL.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 9","pages":"2215-2225"},"PeriodicalIF":13.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02679-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640350","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}
LeukemiaPub Date : 2025-07-16DOI: 10.1038/s41375-025-02695-3
Eric J. Vick, Aishlin Hassan, Kwangmin Choi, Joshua Bennett, Tomoya Muto, Courtnee A. Clough, Ashley E. Culver-Cochran, Kathleen Hueneman, Lyndsey C. Bolanos, Mark Wunderlich, Xiaohu Zhang, Crystal McKnight, Michele Ceribelli, David Holland, Carleen Klumpp-Thomas, Kenneth D. Greis, Craig J. Thomas, Daniel T. Starczynowski
{"title":"Targeting of IRAK4 and GSPT1 enhances therapeutic efficacy in AML via c-Myc destabilization","authors":"Eric J. Vick, Aishlin Hassan, Kwangmin Choi, Joshua Bennett, Tomoya Muto, Courtnee A. Clough, Ashley E. Culver-Cochran, Kathleen Hueneman, Lyndsey C. Bolanos, Mark Wunderlich, Xiaohu Zhang, Crystal McKnight, Michele Ceribelli, David Holland, Carleen Klumpp-Thomas, Kenneth D. Greis, Craig J. Thomas, Daniel T. Starczynowski","doi":"10.1038/s41375-025-02695-3","DOIUrl":"10.1038/s41375-025-02695-3","url":null,"abstract":"IRAK4 is a therapeutic target in myeloid malignancies, but current IRAK4 inhibitors show only modest clinical efficacy in acute myeloid leukemia, highlighting the need for combination strategies. To identify drugs with synergistic potential alongside IRAK4 inhibitors, we conducted a high-throughput screen of 2803 investigational and approved drugs in isogenic IRAK4-deficient and wild-type human AML cells. The top hit from this screen was the Cereblon E3 ligase modulator (CELMoD) CC-885. Validation in vitro and in vivo confirmed that CC-885 and related CELMoDs synergize with IRAK4 inhibitors to suppress leukemic cells. Among CC-885 substrates, GSPT1 loss showed the most pronounced effects in IRAK4-inhibited leukemic cells. Transcriptional and proteomic analyses revealed that CC-885 treatment led to c-Myc suppression in IRAK4-deficient leukemic cells. GSPT1 loss reduces translation efficiency, particularly for proteins with short half-lives, such as c-Myc. Accelerated c-Myc protein loss was confirmed following GSPT1 degradation in leukemic cells, with decreased protein stability observed following inhibition of IRAK4. These effects were validated in AML patient cells, supporting the potential of IRAK4 inhibitors to modulate c-Myc activity and enhance combinatorial therapies. This study demonstrates that IRAK4 is a therapeutic target in AML, and that combination therapies, such as with certain GSPT1-targeting CELMoDs, will be necessary to achieve maximal clinical responses.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 9","pages":"2163-2173"},"PeriodicalIF":13.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02695-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640351","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}
LeukemiaPub Date : 2025-07-15DOI: 10.1038/s41375-025-02704-5
Gaurav Goyal, Aldo A. Acosta-Medina, Ronald S. Go, Jithma P. Abeykoon, on behalf of the Mayo Clinic - University of Alabama at Birmingham Histiocytosis Working Group
{"title":"Molecular profiling is critical to guide MEK inhibitor use in Erdheim-Chester disease","authors":"Gaurav Goyal, Aldo A. Acosta-Medina, Ronald S. Go, Jithma P. Abeykoon, on behalf of the Mayo Clinic - University of Alabama at Birmingham Histiocytosis Working Group","doi":"10.1038/s41375-025-02704-5","DOIUrl":"10.1038/s41375-025-02704-5","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 9","pages":"2306-2307"},"PeriodicalIF":13.4,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629673","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 : 2025-07-14DOI: 10.1038/s41375-025-02680-w
Simge Kelekçi, Katherine Kelly, Ashish Goyal, Nick Wehrwein, Anna Riedel, Dieter Weichenhan, Michael Scherer, Birgitta E. Michels, Cindy Körner, Irene Orzella, Mariam Hakobyan, Marion Bähr, Elena Everatt, James Dunford, Daniel B. Lipka, Pavlo Lutsik, Udo Oppermann, Christoph Plass
{"title":"DNA demethylation-mediated downregulation of MNX1 in acute myeloid leukemia","authors":"Simge Kelekçi, Katherine Kelly, Ashish Goyal, Nick Wehrwein, Anna Riedel, Dieter Weichenhan, Michael Scherer, Birgitta E. Michels, Cindy Körner, Irene Orzella, Mariam Hakobyan, Marion Bähr, Elena Everatt, James Dunford, Daniel B. Lipka, Pavlo Lutsik, Udo Oppermann, Christoph Plass","doi":"10.1038/s41375-025-02680-w","DOIUrl":"10.1038/s41375-025-02680-w","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 9","pages":"2270-2274"},"PeriodicalIF":13.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02680-w.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622353","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}
{"title":"A novel approach for highly sensitive and rapid identification of HMGA2 submicroscopic deletions in myeloproliferative neoplasms","authors":"Niccolò Bartalucci, Danilo Tarantino, Alessio Enderti, Daniele Colazzo, Paola Guglielmelli, Alessandro M. Vannucchi","doi":"10.1038/s41375-025-02678-4","DOIUrl":"10.1038/s41375-025-02678-4","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 8","pages":"2042-2045"},"PeriodicalIF":13.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02678-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144622217","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}
LeukemiaPub Date : 2025-07-14DOI: 10.1038/s41375-025-02701-8
Saurabh Zanwar, S. Vincent Rajkumar
{"title":"Solitary but not simple─a call for precision risk stratification and individualized treatment in solitary plasmacytoma","authors":"Saurabh Zanwar, S. Vincent Rajkumar","doi":"10.1038/s41375-025-02701-8","DOIUrl":"10.1038/s41375-025-02701-8","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"39 9","pages":"2047-2048"},"PeriodicalIF":13.4,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41375-025-02701-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144630350","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}
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