Pub Date : 2026-02-04DOI: 10.1038/s41375-026-02876-8
Theresa Rohm, Konrad Bochennek, Isabel Taeuber, Jan-Henning Klusmann, Anke Barnbrock, Thomas Lehrnbecher
{"title":"Safety and efficacy of short courses of antibiotic therapy in high-risk febrile neutropenic pediatric patients","authors":"Theresa Rohm, Konrad Bochennek, Isabel Taeuber, Jan-Henning Klusmann, Anke Barnbrock, Thomas Lehrnbecher","doi":"10.1038/s41375-026-02876-8","DOIUrl":"https://doi.org/10.1038/s41375-026-02876-8","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"15 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115769","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}
Pub Date : 2026-02-04DOI: 10.1038/s41375-026-02872-y
Zhi-Zhang Yang, Hyo Jin Kim, Xinyi Tang, Joseph P. Novak, Vaishali Bhardwaj, Prithviraj Mukherjee, Jose C. Villasboas, Anne J. Novak, Patrizia Mondello, Stephen M. Ansell
{"title":"Malignant B cells expressing SIRPα are highly proliferative and are associated with inferior clinical outcomes in B-cell non-Hodgkin lymphoma","authors":"Zhi-Zhang Yang, Hyo Jin Kim, Xinyi Tang, Joseph P. Novak, Vaishali Bhardwaj, Prithviraj Mukherjee, Jose C. Villasboas, Anne J. Novak, Patrizia Mondello, Stephen M. Ansell","doi":"10.1038/s41375-026-02872-y","DOIUrl":"https://doi.org/10.1038/s41375-026-02872-y","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"9 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-02-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146115768","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}
Pub Date : 2026-02-03DOI: 10.1038/s41375-026-02877-7
Alberto Guijosa, Nicholas Tsakmaklis, Margaret Kobs, Amanda Kofides, Maria Luisa Guerrera, Gottfried von Keudell, Andrew Branagan, Zachary R. Hunter, Steven P. Treon, Shayna Sarosiek, Jorge J. Castillo
{"title":"Off-trial outcomes of zanubrutinib in Waldenström macroglobulinemia: the prognostic impact of CXCR4 and TP53 alterations","authors":"Alberto Guijosa, Nicholas Tsakmaklis, Margaret Kobs, Amanda Kofides, Maria Luisa Guerrera, Gottfried von Keudell, Andrew Branagan, Zachary R. Hunter, Steven P. Treon, Shayna Sarosiek, Jorge J. Castillo","doi":"10.1038/s41375-026-02877-7","DOIUrl":"https://doi.org/10.1038/s41375-026-02877-7","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"87 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102078","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}
Pub Date : 2026-02-03DOI: 10.1038/s41375-026-02871-z
Xiaoli Wang, Andrew Davis, Cing Siang Hu, Fei Huang, Sophia Jiang, John Mascarenhas, Ronald Hoffman
{"title":"Sequential treatment with ruxolitinib and imetelstat effectively depletes myelofibrosis hematopoietic stem and progenitor cells","authors":"Xiaoli Wang, Andrew Davis, Cing Siang Hu, Fei Huang, Sophia Jiang, John Mascarenhas, Ronald Hoffman","doi":"10.1038/s41375-026-02871-z","DOIUrl":"https://doi.org/10.1038/s41375-026-02871-z","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"290 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102079","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}
Pub Date : 2026-02-03DOI: 10.1038/s41375-026-02879-5
Jennifer Fraszczak, Charles Vadnais, Marissa Rashkovan, Julie Ross, Hugues Beauchemin, Riyan Chen, Damien Grapton, Cyrus Khandanpour, Tarik Möröy
{"title":"Correction: Reduced expression but not deficiency of GFI1 causes a fatal myeloproliferative disease in mice.","authors":"Jennifer Fraszczak, Charles Vadnais, Marissa Rashkovan, Julie Ross, Hugues Beauchemin, Riyan Chen, Damien Grapton, Cyrus Khandanpour, Tarik Möröy","doi":"10.1038/s41375-026-02879-5","DOIUrl":"https://doi.org/10.1038/s41375-026-02879-5","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":" ","pages":""},"PeriodicalIF":13.4,"publicationDate":"2026-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146113635","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}
Pub Date : 2026-02-02DOI: 10.1038/s41375-025-02843-9
David Kealy, Ruth Ellerington, Suraj Bansal, Jessie J. F. Medeiros, Catherine A. Hawley, Andy G. X. Zeng, Jakub Lukaszonek, Katie A. West, Aparna D. Sinha, Gillian Caalim, Richard T. Gawne, Jacob Pope, Bianca Lima Ferreira, Nicole-Mae Blacknell, Bryce Drylie, Jenny Chatzigerou, Hwei Minn Khoo, Adam C. Wilkinson, Adele K. Fielding, Guanlin Wang, Bethan Psaila, David G. Kent, Ian S. Hitchcock, Andrew N. Holding, Andrew S. Mason, Vikas Gupta, John E. Dick, Katherine S. Bridge
Hypoxia-inducible factors (HIFs) are master transcriptional regulators, central to cellular survival in hypoxia and frequently activated within malignancy. Whilst malignant context directs the role of HIFs within oncogenesis, these mechanisms are not well characterised. Applying the JAK2V617F myeloproliferative neoplasms (MPNs) oncogene-driver model, in which HIF-1α is stabilised in normoxia (20% O2), we sought to determine whether the modality of HIF-1 activation directs its function. Through direct analysis of hypoxia-activated vs. JAK2V617F-activated HIF-1 at the chromatin, we define a JAK2V617F-HIF-1 regulon that diverges from canonical HIF/hypoxia targets. In a cohort of 172 JAK2V617F-MPN patients, we observe significant association of the JAK2V617F-HIF-1 regulon, but not canonical HIF-1 gene signatures, with disease severity, progression, and patient survival. We further define a subset gene signature (HIF1-MPN-BP) significantly associated with spontaneous transformation to blast phase MPNs. Finally, we identify that JAK2V617F-induced HIF-1α stabilisation is mediated via PIM1 kinase. Our findings demonstrate that HIF-1 activation by the JAK2V617F-PIM1 axis significantly alters HIF-1 transcription function, desensitising HIF-1 activity to cellular oxygen levels, and restricting the HIF-1 regulon to a set of disease-associated target genes within JAK2V617F-MPNs. These findings restore the potential for specific therapeutic targeting of HIF-1 by delineating malignant activation from the physiological hypoxic response.
{"title":"JAK2V617F reprograms Hypoxia Inducible Factor-1 to induce a non-canonical hypoxia regulon in myeloproliferative neoplasms","authors":"David Kealy, Ruth Ellerington, Suraj Bansal, Jessie J. F. Medeiros, Catherine A. Hawley, Andy G. X. Zeng, Jakub Lukaszonek, Katie A. West, Aparna D. Sinha, Gillian Caalim, Richard T. Gawne, Jacob Pope, Bianca Lima Ferreira, Nicole-Mae Blacknell, Bryce Drylie, Jenny Chatzigerou, Hwei Minn Khoo, Adam C. Wilkinson, Adele K. Fielding, Guanlin Wang, Bethan Psaila, David G. Kent, Ian S. Hitchcock, Andrew N. Holding, Andrew S. Mason, Vikas Gupta, John E. Dick, Katherine S. Bridge","doi":"10.1038/s41375-025-02843-9","DOIUrl":"https://doi.org/10.1038/s41375-025-02843-9","url":null,"abstract":"Hypoxia-inducible factors (HIFs) are master transcriptional regulators, central to cellular survival in hypoxia and frequently activated within malignancy. Whilst malignant context directs the role of HIFs within oncogenesis, these mechanisms are not well characterised. Applying the JAK2V617F myeloproliferative neoplasms (MPNs) oncogene-driver model, in which HIF-1α is stabilised in normoxia (20% O2), we sought to determine whether the modality of HIF-1 activation directs its function. Through direct analysis of hypoxia-activated vs. JAK2V617F-activated HIF-1 at the chromatin, we define a JAK2V617F-HIF-1 regulon that diverges from canonical HIF/hypoxia targets. In a cohort of 172 JAK2V617F-MPN patients, we observe significant association of the JAK2V617F-HIF-1 regulon, but not canonical HIF-1 gene signatures, with disease severity, progression, and patient survival. We further define a subset gene signature (HIF1-MPN-BP) significantly associated with spontaneous transformation to blast phase MPNs. Finally, we identify that JAK2V617F-induced HIF-1α stabilisation is mediated via PIM1 kinase. Our findings demonstrate that HIF-1 activation by the JAK2V617F-PIM1 axis significantly alters HIF-1 transcription function, desensitising HIF-1 activity to cellular oxygen levels, and restricting the HIF-1 regulon to a set of disease-associated target genes within JAK2V617F-MPNs. These findings restore the potential for specific therapeutic targeting of HIF-1 by delineating malignant activation from the physiological hypoxic response.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"14 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146102075","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}
Pub Date : 2026-01-29DOI: 10.1038/s41375-026-02864-y
Junren Chen,Robert Peter Gale
{"title":"Physician-complementing artificial intelligence in haematology: ushering in a new era.","authors":"Junren Chen,Robert Peter Gale","doi":"10.1038/s41375-026-02864-y","DOIUrl":"https://doi.org/10.1038/s41375-026-02864-y","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"14 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072990","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}
Pub Date : 2026-01-26DOI: 10.1038/s41375-025-02849-3
Claus-Moritz Gräf, Moritz Reese, Angela Vicente-Luque, Nicolas Mönig, Charlotte Bruzeau, Ferran Nadeu, Maria Latacz, Johanna Bihler, Jörn Meinel, Maria Cartolano, Martin Peifer, Sílvia Beà, Elias Campo, Melanie Thelen, Paul J. Bröckelmann, Ron D. Jachimowicz
{"title":"Establishment and characterization of a CCND1-rearranged non-mantle cell lymphoma cell line and patient-derived xenograft model","authors":"Claus-Moritz Gräf, Moritz Reese, Angela Vicente-Luque, Nicolas Mönig, Charlotte Bruzeau, Ferran Nadeu, Maria Latacz, Johanna Bihler, Jörn Meinel, Maria Cartolano, Martin Peifer, Sílvia Beà, Elias Campo, Melanie Thelen, Paul J. Bröckelmann, Ron D. Jachimowicz","doi":"10.1038/s41375-025-02849-3","DOIUrl":"https://doi.org/10.1038/s41375-025-02849-3","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"41 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146048366","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}
Pub Date : 2026-01-23DOI: 10.1038/s41375-025-02852-8
Vivian G Oehler,Olga Sala-Torra,Neta Gilderman,Lan Beppu,David W Woolston,Priscilla Namaganda,Jennifer Rynning,Inés García González,Andrea Towlerton,Jenna Voutsinas,Qian Wu,Cecilia C S Yeung,Jerald P Radich
The goal of the "Spot On CML" program is to provide diagnostic and monitoring tests to chronic myeloid leukemia (CML) patients in low- and middle-income countries (LMICs). Previously, we demonstrated reproducible BCR::ABL1 transcript quantification using dried blood spots (DBS). We have now optimized methods of DNA and RNA extraction from DBS, allowing the detection of myeloid gene variants, including ABL1 tyrosine kinase domain mutations. Among 177 CML patients from nine countries, ABL1 mutations were identified in 61 (34%) patients, with multiple mutations present in some cases. The most common ABL1 mutation was T315I (45.9% of patients with ABL1 mutations). Among 69 patients, 89 Tier I-II variants (pathogenic or likely pathogenic) were identified in other genes, including 52 ASXL1 variants in 49 patients. The detection of ASXL1 variants correlated strongly with the presence of ABL1 mutations (P = 3.51E-04). These methodologies are directly applicable to all assays used for the diagnosis, prognosis, and monitoring of CML and have important implications in bringing state-of-the-art genetic analysis to CML patients in LMICs.
{"title":"Next-generation sequencing from chronic myeloid leukemia dried blood spots: insights and implications for global oncology.","authors":"Vivian G Oehler,Olga Sala-Torra,Neta Gilderman,Lan Beppu,David W Woolston,Priscilla Namaganda,Jennifer Rynning,Inés García González,Andrea Towlerton,Jenna Voutsinas,Qian Wu,Cecilia C S Yeung,Jerald P Radich","doi":"10.1038/s41375-025-02852-8","DOIUrl":"https://doi.org/10.1038/s41375-025-02852-8","url":null,"abstract":"The goal of the \"Spot On CML\" program is to provide diagnostic and monitoring tests to chronic myeloid leukemia (CML) patients in low- and middle-income countries (LMICs). Previously, we demonstrated reproducible BCR::ABL1 transcript quantification using dried blood spots (DBS). We have now optimized methods of DNA and RNA extraction from DBS, allowing the detection of myeloid gene variants, including ABL1 tyrosine kinase domain mutations. Among 177 CML patients from nine countries, ABL1 mutations were identified in 61 (34%) patients, with multiple mutations present in some cases. The most common ABL1 mutation was T315I (45.9% of patients with ABL1 mutations). Among 69 patients, 89 Tier I-II variants (pathogenic or likely pathogenic) were identified in other genes, including 52 ASXL1 variants in 49 patients. The detection of ASXL1 variants correlated strongly with the presence of ABL1 mutations (P = 3.51E-04). These methodologies are directly applicable to all assays used for the diagnosis, prognosis, and monitoring of CML and have important implications in bringing state-of-the-art genetic analysis to CML patients in LMICs.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"50 1","pages":""},"PeriodicalIF":11.4,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146034048","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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