LeukemiaPub Date : 2025-05-07DOI: 10.1038/s41375-025-02629-z
Sandra Novoa-Jáuregui, Sandra Huber, Maria Gabarrós-Subirà, Tzu Hua Chen-Liang, Sara Torres-Esquius, Salvador Carrillo-Tornel, Marta Santiago, Teresa Bernal del Castillo, Iván Martín-Castillo, Francisca Maria Hernandez, Mónica del Rey, Alessandro Liquori, Mar Tormo, Jose Cervera, Francesc Bosch, David Valcárcel, Claudia Haferlach, María Díez-Campelo, María Julia Montoro, Torsten Haferlach, Andrés Jerez
{"title":"Myelodysplastic neoplasms with ring sideroblasts without SF3B1 mutations in adults: enrichment of germline variants in congenital sideroblastic anemia genes","authors":"Sandra Novoa-Jáuregui, Sandra Huber, Maria Gabarrós-Subirà, Tzu Hua Chen-Liang, Sara Torres-Esquius, Salvador Carrillo-Tornel, Marta Santiago, Teresa Bernal del Castillo, Iván Martín-Castillo, Francisca Maria Hernandez, Mónica del Rey, Alessandro Liquori, Mar Tormo, Jose Cervera, Francesc Bosch, David Valcárcel, Claudia Haferlach, María Díez-Campelo, María Julia Montoro, Torsten Haferlach, Andrés Jerez","doi":"10.1038/s41375-025-02629-z","DOIUrl":"https://doi.org/10.1038/s41375-025-02629-z","url":null,"abstract":"<p>Ring sideroblasts (RS) are erythroid precursors with pathological, iron-laden mitochondria, exposed by Prussian blue staining as a perinuclear ring of blue granules [1]. RS can be seen in non-clonal (toxic or metabolic) and clonal disorders (congenital sideroblastic anemias and acquired myeloid neoplasms) [2]. Myelodysplastic neoplasms (MDS) account for the majority of RS cases, and their presence has been a defining feature of MDS in the World Health Organization (WHO) classification since 2002 [3]. In 2011, a high proportion of MDS-RS patients were found to be somatically mutated in <i>SF3B1</i> [4]. However, approximately 20% of cases lack the <i>SF3B1</i> mutation (<i>SF3B1</i><sup>wt</sup> MDS-RS) without clear evidence regarding the molecular driver event [5,6,7].</p><p>On the other hand, congenital forms of sideroblastic anemia (CSA) are uncommon, with variable inheritance patterns and causative genes involved in heme biosynthesis [2]. They are diagnosed usually within the first two decades of life. Nevertheless, a “second hit”, such as acquired skewed X-chromosome inactivation, can lead to diagnoses in mid to late adulthood in women carrying mutations in the erythroid-specific isoform of aminolevulinic acid synthase 2 (<i>ALAS2</i>), causing the most common CSA, the X-linked sideroblastic anemia (XLSA). These cases encompass one-quarter of clinically affected XLSA probands and have led to what have been considered <i>SF3B1</i><sup>wt</sup> MDS-RS misdiagnoses [8,9,10].</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"14 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916001","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 : 2025-05-07DOI: 10.1038/s41375-025-02635-1
Ryan J. Stubbins, Stephen Arnovitz, Jennie Vagher, Anase Asom, Melody Perpich, Madeline Pies, Imo J. Akpan, Edward Chew, Joshua Bridgers, Aly Karsan, Courtnee Rodgers, Ashwin Koppayi, Hatice Basdag, Michael W. Drazer, Soma Das, Jason Cheng, Afaf E. G. Osman, Lucy A. Godley
{"title":"Predisposition to hematopoietic malignancies by deleterious germline CHEK2 variants","authors":"Ryan J. Stubbins, Stephen Arnovitz, Jennie Vagher, Anase Asom, Melody Perpich, Madeline Pies, Imo J. Akpan, Edward Chew, Joshua Bridgers, Aly Karsan, Courtnee Rodgers, Ashwin Koppayi, Hatice Basdag, Michael W. Drazer, Soma Das, Jason Cheng, Afaf E. G. Osman, Lucy A. Godley","doi":"10.1038/s41375-025-02635-1","DOIUrl":"https://doi.org/10.1038/s41375-025-02635-1","url":null,"abstract":"<p>The role of germline <i>CHEK2</i> variants in hematopoietic malignancies (HMs) is poorly understood. We examined pathogenic/likely pathogenic (P/LP) <i>CHEK2</i> variants in patients with hereditary HMs (HHMs), a solid tumor risk cohort, public datasets, and a knock-in mouse model. In the HHM cohort, 57 probands had germline P/LP <i>CHEK2</i> variants, mostly p.I157T (53%, 30/57). Among <i>CHEK2</i> p.I157T carriers, 43% (19/44) had myeloid malignancies, 32% (14/44) had lymphoid malignancies, and 2% (1/44) had both. Among those with other germline P/LP <i>CHEK2</i> alleles, 36% (13/36) had myeloid malignancies, 28% (10/36) had lymphoid malignancies, and 6% (2/36) had both. <i>CHEK2</i> p.I157T was enriched in HM patients (OR 6.44, 95%CI 3.68–10.73, <i>P</i> < 0.001). In a solid tumor risk cohort, 36% (15/42) of <i>CHEK2</i> p.I157T patients had a HM family history. A genome wide association study showed enrichment of <i>CHEK2</i> loss-of-function variants with myeloid leukemia (<i>P</i> = 5.78e<sup>−7</sup>). In public acute myeloid leukemia (AML) datasets, 1% (16/1348) of patients had P/LP <i>CHEK2</i> variants. In a public myelodysplastic neoplasms (MDS) dataset, 2% (5/214) had P/LP <i>CHEK2</i> variants. <i>Chek2</i> p.I161T mice, homologous to human p.I157T, had worse survival as heterozygotes (<i>P</i> = 0.037) or homozygotes (<i>P</i> = 0.005), with fewer Lin-CD34+ and Lin-cKit+ cells. Our data suggest P/LP <i>CHEK2</i> variants are HHM risk alleles.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"103 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916002","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 : 2025-05-05DOI: 10.1038/s41375-025-02637-z
Le Xuan Truong Nguyen, Bin Zhang, Dinh Hoa Hoang, Dandan Zhao, Huafeng Wang, Herman Wu, Yu-Lin Su, Haojie Dong, Sonia Rodriguez-Rodriguez, Brian Armstrong, Lucy Y Ghoda, Danilo Perrotti, Flavia Pichiorri, Jianjun Chen, Ling Li, Marcin Kortylewski, Russell C Rockne, Ya-Huei Kuo, Samer Khaled, Nadia Carlesso, Guido Marcucci
{"title":"Correction: Cytoplasmic DROSHA and non-canonical mechanisms of MiR-155 biogenesis in FLT3-ITD acute myeloid leukemia.","authors":"Le Xuan Truong Nguyen, Bin Zhang, Dinh Hoa Hoang, Dandan Zhao, Huafeng Wang, Herman Wu, Yu-Lin Su, Haojie Dong, Sonia Rodriguez-Rodriguez, Brian Armstrong, Lucy Y Ghoda, Danilo Perrotti, Flavia Pichiorri, Jianjun Chen, Ling Li, Marcin Kortylewski, Russell C Rockne, Ya-Huei Kuo, Samer Khaled, Nadia Carlesso, Guido Marcucci","doi":"10.1038/s41375-025-02637-z","DOIUrl":"https://doi.org/10.1038/s41375-025-02637-z","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144001177","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 : 2025-05-02DOI: 10.1038/s41375-025-02631-5
Yuta Ito, Joji Shimono, Keisuke Kawamoto, Kanako C. Hatanaka, Yasunori Kogure, Mariko Tabata, Yuki Saito, Kota Mizuno, Sara Horie, Yosuke Mizukami, Junji Koya, Koichi Murakami, Takanori Teshima, Yutaka Hatanaka, Kenichi Chiba, Ai Okada, Yuichi Shiraishi, Hiroaki Miyoshi, Yoshihiro Matsuno, Koichi Ohshima, Keisuke Kataoka, Masao Nakagawa
{"title":"TP53 and CDKN2A alterations define a poor prognostic subgroup in patients with nodal T follicular helper cell lymphoma","authors":"Yuta Ito, Joji Shimono, Keisuke Kawamoto, Kanako C. Hatanaka, Yasunori Kogure, Mariko Tabata, Yuki Saito, Kota Mizuno, Sara Horie, Yosuke Mizukami, Junji Koya, Koichi Murakami, Takanori Teshima, Yutaka Hatanaka, Kenichi Chiba, Ai Okada, Yuichi Shiraishi, Hiroaki Miyoshi, Yoshihiro Matsuno, Koichi Ohshima, Keisuke Kataoka, Masao Nakagawa","doi":"10.1038/s41375-025-02631-5","DOIUrl":"https://doi.org/10.1038/s41375-025-02631-5","url":null,"abstract":"<p>Nodal T follicular helper cell lymphoma (nTFHL) exhibits unique immunophenotypes and somatic alterations, while the prognostic value of these alterations remains unclear. By analyzing 173 nTFHL cases, we identified 36 driver genes, including 4 novel ones (<i>TET3</i>, <i>HLA-C</i>, <i>NRAS</i>, and <i>KLF2</i>). Then, we classified nTFHL cases into four molecular subgroups by major driver alterations. TR-I (+) and TR-I (−) were characterized by <i>TET2</i> and/or <i>RHOA</i> mutations with and without <i>IDH2</i> mutations; AC53 by <i>TP53</i> and/or <i>CDKN2A</i> alterations and aneuploidy; and NSD with no subgroup-defining alterations (namely without any of the above alterations). AC53 exhibited the worst survival, while NSD, particularly those lacking driver alterations, showed the best prognosis. nTFHL had a better prognosis than peripheral T-cell lymphoma, not otherwise specified, when <i>TP53</i> and/or <i>CDKN2A</i> alterations were absent. Multivariable analyses showed that AC53, the presence of driver alterations, and international prognostic index high-risk were independently associated with worse survival. Finally, we developed a simple prognostic index (mTFHL-PI), which classified patients into three risk categories with a median OS of 181, 67, and 20 months, respectively. Our study identifies novel prognostic factors, namely <i>TP53</i> and/or <i>CDKN2A</i> alterations and the presence of driver alterations, demonstrating the clinical relevance of molecular classification in nTFHL.</p>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"14 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143898076","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 : 2025-05-01DOI: 10.1038/s41375-025-02597-4
P J Bröckelmann, H Müller, M Fuchs, S Gillessen, D A Eichenauer, S Borchmann, A S Robertz, K Behringer, J Welters, J Ferdinandus, B Böll, H Tharmaseelan, X Yang, C Kobe, H T Eich, C Baues, W Klapper, P Borchmann, B von Tresckow
{"title":"Correction: Correlation of progression-free survival and overall survival after treatment for relapsed Hodgkin lymphoma: individual patient data analysis of randomized German Hodgkin Study Group (GHSG) Trials.","authors":"P J Bröckelmann, H Müller, M Fuchs, S Gillessen, D A Eichenauer, S Borchmann, A S Robertz, K Behringer, J Welters, J Ferdinandus, B Böll, H Tharmaseelan, X Yang, C Kobe, H T Eich, C Baues, W Klapper, P Borchmann, B von Tresckow","doi":"10.1038/s41375-025-02597-4","DOIUrl":"10.1038/s41375-025-02597-4","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":"1274"},"PeriodicalIF":12.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12055578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753484","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 : 2025-04-29DOI: 10.1038/s41375-025-02630-6
Syed A. Mian, Steven Ngo, Dominique Bonnet
{"title":"Is the bone marrow microenvironment the hidden catalyst in malignant haematopoiesis?","authors":"Syed A. Mian, Steven Ngo, Dominique Bonnet","doi":"10.1038/s41375-025-02630-6","DOIUrl":"https://doi.org/10.1038/s41375-025-02630-6","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"18 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143890061","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 : 2025-04-29DOI: 10.1038/s41375-025-02612-8
Andreas O. Mieland, Giuseppe Petrosino, Mario Dejung, Jia-Xuan Chen, Amitkumar Fulzele, Fereshteh Mahmoudi, Jia-Wey Tu, Al-Hassan M. Mustafa, Yanira Zeyn, Christoph Hieber, Matthias Bros, Tina M. Schnöder, Florian H. Heidel, Sara Najafi, Ina Oehme, Ilse Hofmann, Mike Schutkowski, Sebastian Hilscher, Christian Kosan, Falk Butter, Sanil Bhatia, Wolfgang Sippl, Oliver H. Krämer
{"title":"The protein deacetylase HDAC10 controls DNA replication in malignant lymphoid cells","authors":"Andreas O. Mieland, Giuseppe Petrosino, Mario Dejung, Jia-Xuan Chen, Amitkumar Fulzele, Fereshteh Mahmoudi, Jia-Wey Tu, Al-Hassan M. Mustafa, Yanira Zeyn, Christoph Hieber, Matthias Bros, Tina M. Schnöder, Florian H. Heidel, Sara Najafi, Ina Oehme, Ilse Hofmann, Mike Schutkowski, Sebastian Hilscher, Christian Kosan, Falk Butter, Sanil Bhatia, Wolfgang Sippl, Oliver H. Krämer","doi":"10.1038/s41375-025-02612-8","DOIUrl":"https://doi.org/10.1038/s41375-025-02612-8","url":null,"abstract":"<p>Histone deacetylases (HDACs) comprise a family of 18 epigenetic modifiers. The biologically relevant functions of HDAC10 in leukemia cells are enigmatic. We demonstrate that human cultured and primary acute B cell/T cell leukemia and lymphoma cells require the catalytic activity of HDAC10 for their survival. In such cells, HDAC10 controls a MYC-dependent transcriptional induction of the DNA polymerase subunit POLD1. Consequently, pharmacological inhibition of HDAC10 causes DNA breaks and an accumulation of poly-ADP-ribose chains. These processes culminate in caspase-dependent apoptosis. PZ48 does not damage resting and proliferating human normal blood cells. The in vivo activity of PZ48 against ALL cells is verified in a <i>Danio rerio</i> model. These data reveal a nuclear function for HDAC10. HDAC10 controls the MYC-POLD1 axis to maintain the processivity of DNA replication and genome integrity. This mechanistically defined “HDAC10ness” may be exploited as treatment option for lymphoid malignancies.</p><figure></figure>","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"18 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143884656","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 : 2025-04-28DOI: 10.1038/s41375-025-02627-1
Ioanna Xagoraris, Ying Yang, Erofili Bougka, Dora Trogrlic, Persa Xyderou, Konstantina Stathopoulou, Nikolas Herold, Andreas Lundqvist, George Z. Rassidakis
{"title":"Sulforaphane promotes natural killer cell-mediated anti-tumor immune responses partially via cGAS-STING pathway in classical Hodgkin lymphoma","authors":"Ioanna Xagoraris, Ying Yang, Erofili Bougka, Dora Trogrlic, Persa Xyderou, Konstantina Stathopoulou, Nikolas Herold, Andreas Lundqvist, George Z. Rassidakis","doi":"10.1038/s41375-025-02627-1","DOIUrl":"https://doi.org/10.1038/s41375-025-02627-1","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"153 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880344","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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