Pub Date : 2025-11-21DOI: 10.1038/s41408-025-01417-3
Joel-Sean Hsu, Udit Yadav, Kishore Garapati, Kiran K. Mangalaparthi, Yogesh Chawla, J. Erin Wiedmeier-Nutor, Rafael Fonseca, P. Leif Bergsagel, S. Vincent Rajkumar, Shaji Kumar, Wilson I. Gonsalves, Akhilesh Pandey, Richard K. Kandasamy
{"title":"Defining the proteome of bone marrow plasma in multiple myeloma and monoclonal gammopathy of undetermined significance","authors":"Joel-Sean Hsu, Udit Yadav, Kishore Garapati, Kiran K. Mangalaparthi, Yogesh Chawla, J. Erin Wiedmeier-Nutor, Rafael Fonseca, P. Leif Bergsagel, S. Vincent Rajkumar, Shaji Kumar, Wilson I. Gonsalves, Akhilesh Pandey, Richard K. Kandasamy","doi":"10.1038/s41408-025-01417-3","DOIUrl":"https://doi.org/10.1038/s41408-025-01417-3","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"1 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145567304","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 : 2025-11-19DOI: 10.1038/s41408-025-01426-2
Diva Baggio, Eliza A. Hawkes, Mikkel Runason Simonsen, Tarec Christoffer El-Galaly
{"title":"Opportunities and risks associated with external comparator cohorts in clinical drug development in hematology","authors":"Diva Baggio, Eliza A. Hawkes, Mikkel Runason Simonsen, Tarec Christoffer El-Galaly","doi":"10.1038/s41408-025-01426-2","DOIUrl":"https://doi.org/10.1038/s41408-025-01426-2","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"369 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145553742","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 : 2025-11-17DOI: 10.1038/s41408-025-01391-w
Lena Golick, Reeder M. Robinson, Leticia Reyes, Nadia St. Thomas, Kathleen Klinzing, Erin C. O’Connor, Leonardo M. R. Ferreira, Nathan G. Dolloff
The treatment of acute myeloid leukemia (AML) remains a challenge due to disease heterogeneity, which undermines efforts to develop targeted therapeutics, leaving conventional chemotherapy as the standard of care (SOC). Sialic acid binding Ig-like lectin 3 (CD33) is a myeloid cell surface glycoprotein that is highly expressed on AML blasts. However, while ~90% of AML cases express CD33, 50% of these patients harbor a single nucleotide polymorphism (SNP) that eliminates the antibody binding epitope for existing CD33-targeted antibody therapeutics. In this study, we developed an immunotherapy (M2T-CD33) that targets CD33 directly to MHC class II (MHCII) molecules on antigen presenting cells for enhanced presentation to the immune system. We found that M2T-CD33 induces a robust polyclonal anti-CD33 humoral response composed of the full immunoglobulin repertoire. M2T-CD33 induced an anti-AML response in a syngeneic mouse model that was dependent on CD4+ and CD8+ T cells. The immune response was elicited against both the full length and spliced version of CD33 and showed no evidence of toxicity at concentrations 40-fold higher than the efficacious dose. Finally, M2T-CD33 was enhanced by combinations with anti-PD-1 therapy. These experiments demonstrate the preclinical potential of M2T-CD33 in AML and emphasize the importance of MHCII for cancer immunotherapy.
{"title":"A superantigen-based MHC class II-targeted cancer immunotherapy for the treatment of acute myeloid leukemia","authors":"Lena Golick, Reeder M. Robinson, Leticia Reyes, Nadia St. Thomas, Kathleen Klinzing, Erin C. O’Connor, Leonardo M. R. Ferreira, Nathan G. Dolloff","doi":"10.1038/s41408-025-01391-w","DOIUrl":"https://doi.org/10.1038/s41408-025-01391-w","url":null,"abstract":"The treatment of acute myeloid leukemia (AML) remains a challenge due to disease heterogeneity, which undermines efforts to develop targeted therapeutics, leaving conventional chemotherapy as the standard of care (SOC). Sialic acid binding Ig-like lectin 3 (CD33) is a myeloid cell surface glycoprotein that is highly expressed on AML blasts. However, while ~90% of AML cases express CD33, 50% of these patients harbor a single nucleotide polymorphism (SNP) that eliminates the antibody binding epitope for existing CD33-targeted antibody therapeutics. In this study, we developed an immunotherapy (M2T-CD33) that targets CD33 directly to MHC class II (MHCII) molecules on antigen presenting cells for enhanced presentation to the immune system. We found that M2T-CD33 induces a robust polyclonal anti-CD33 humoral response composed of the full immunoglobulin repertoire. M2T-CD33 induced an anti-AML response in a syngeneic mouse model that was dependent on CD4+ and CD8+ T cells. The immune response was elicited against both the full length and spliced version of CD33 and showed no evidence of toxicity at concentrations 40-fold higher than the efficacious dose. Finally, M2T-CD33 was enhanced by combinations with anti-PD-1 therapy. These experiments demonstrate the preclinical potential of M2T-CD33 in AML and emphasize the importance of MHCII for cancer immunotherapy.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"5 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145532018","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 : 2025-11-06DOI: 10.1038/s41408-025-01385-8
Nicholas J. Boddicker, Tait D. Shanafelt, Sameer A. Parikh, Kari G. Rabe, Rosalie Griffin, Aaron D. Norman, Yuan Yao, Shulan Tian, Tao Ma, Daniel R. O’Brien, Bryan A. Vallejo, Mingma S. Hoel, Stacey J. Lehman, Janet E. Olson, Paul J. Hampel, Esteban Braggio, Mrinal M. Patnaik, James R. Cerhan, Celine M. Vachon, Curtis A. Hanson, Susan L. Slager
Monoclonal B-cell lymphocytosis (MBL) and clonal hematopoiesis of indeterminate potential (CHIP) are prevalent clonal precursors associated with increased risk of lymphoid malignancies. However, the relationship between MBL and CHIP and their combined impact on lymphoid malignancy risk remains poorly understood. We screened participants from the Mayo Clinic Biobank to identify MBL using eight-color flow cytometry; CHIP was detected using whole-exome sequencing of whole-blood DNA in 291 genes related to myeloid or lymphoid malignancies. Incident myeloid or lymphoid hematological malignancies were identified using ICD codes and confirmed via medical record review. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Cox regression was used to estimate hazard ratios (HR). Analyses were adjusted for age and sex. In 10,067 participants, 15% had MBL, and 9% had CHIP. No evidence of an association between MBL and CHIP (OR = 1.00; 95% CI: 0.82–1.20) was observed. With a median follow-up of 5.4 years, 138 participants developed hematological malignancies (94 lymphoid). MBL (HR = 3.48; 95% CI: 2.27–5.34; P < 0.001) and CHIP (HR = 1.89; 95% CI: 1.10–3.27; P = 0.022) were each associated with incident lymphoid malignancy. Compared to individuals with no precursors, the combined presence of MBL and CHIP significantly amplified lymphoma risk (HR = 7.18; 95% CI: 3.33–15.47; P < 0.001), more than doubling the risk among individuals with MBL alone (HR = 3.30; 95% CI: 2.06–5.30; P < 0.001). In contrast, the risk associated with CHIP alone was attenuated and no longer statistically significant (HR = 1.63; 95% CI: 0.77–3.47; P = 0.20). MBL and CHIP are independent hematological precursor conditions. While their combined presence amplifies the risk of lymphoid malignancy, CHIP alone may not be a strong independent risk factor.
单克隆b细胞淋巴细胞增多症（MBL）和不确定潜力的克隆造血（CHIP）是与淋巴细胞恶性肿瘤风险增加相关的普遍克隆前体。然而，MBL和CHIP之间的关系以及它们对淋巴细胞恶性肿瘤风险的综合影响仍然知之甚少。我们筛选来自梅奥诊所生物库的参与者，使用八色流式细胞术鉴定MBL；通过对291个髓系或淋巴系恶性肿瘤相关基因的全血DNA全外显子组测序检测CHIP。使用ICD代码识别髓系或淋巴系恶性血液病，并通过病历审查确认。采用Logistic回归估计优势比（OR）和95%置信区间（CI）。采用Cox回归估计风险比（HR）。分析根据年龄和性别进行了调整。在10067名参与者中，15%患有MBL， 9%患有CHIP。没有证据表明MBL和CHIP之间存在关联（OR = 1.00; 95% CI: 0.82-1.20）。在平均5.4年的随访中，138名参与者出现了血液系统恶性肿瘤（94名淋巴细胞）。MBL （HR = 3.48; 95% CI: 2.27-5.34; P < 0.001）和CHIP （HR = 1.89; 95% CI: 1.10-3.27; P = 0.022）均与淋巴细胞恶性肿瘤相关。与没有前体的个体相比，MBL和CHIP的联合存在显著增加了淋巴瘤的风险（HR = 7.18; 95% CI: 3.33-15.47; P < 0.001），单独患有MBL的个体的风险增加了一倍多（HR = 3.30; 95% CI: 2.06-5.30; P < 0.001）。相比之下，单独与CHIP相关的风险减弱，不再具有统计学意义（HR = 1.63; 95% CI: 0.77-3.47; P = 0.20）。MBL和CHIP是独立的血液学前体疾病。虽然它们的联合存在会增加淋巴细胞恶性肿瘤的风险，但CHIP本身可能不是一个强大的独立风险因素。
{"title":"CHIP amplifies the risk of lymphoid malignancies in individuals with monoclonal B-cell lymphocytosis (MBL)","authors":"Nicholas J. Boddicker, Tait D. Shanafelt, Sameer A. Parikh, Kari G. Rabe, Rosalie Griffin, Aaron D. Norman, Yuan Yao, Shulan Tian, Tao Ma, Daniel R. O’Brien, Bryan A. Vallejo, Mingma S. Hoel, Stacey J. Lehman, Janet E. Olson, Paul J. Hampel, Esteban Braggio, Mrinal M. Patnaik, James R. Cerhan, Celine M. Vachon, Curtis A. Hanson, Susan L. Slager","doi":"10.1038/s41408-025-01385-8","DOIUrl":"https://doi.org/10.1038/s41408-025-01385-8","url":null,"abstract":"Monoclonal B-cell lymphocytosis (MBL) and clonal hematopoiesis of indeterminate potential (CHIP) are prevalent clonal precursors associated with increased risk of lymphoid malignancies. However, the relationship between MBL and CHIP and their combined impact on lymphoid malignancy risk remains poorly understood. We screened participants from the Mayo Clinic Biobank to identify MBL using eight-color flow cytometry; CHIP was detected using whole-exome sequencing of whole-blood DNA in 291 genes related to myeloid or lymphoid malignancies. Incident myeloid or lymphoid hematological malignancies were identified using ICD codes and confirmed via medical record review. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Cox regression was used to estimate hazard ratios (HR). Analyses were adjusted for age and sex. In 10,067 participants, 15% had MBL, and 9% had CHIP. No evidence of an association between MBL and CHIP (OR = 1.00; 95% CI: 0.82–1.20) was observed. With a median follow-up of 5.4 years, 138 participants developed hematological malignancies (94 lymphoid). MBL (HR = 3.48; 95% CI: 2.27–5.34; <jats:italic>P</jats:italic> < 0.001) and CHIP (HR = 1.89; 95% CI: 1.10–3.27; <jats:italic>P</jats:italic> = 0.022) were each associated with incident lymphoid malignancy. Compared to individuals with no precursors, the combined presence of MBL and CHIP significantly amplified lymphoma risk (HR = 7.18; 95% CI: 3.33–15.47; <jats:italic>P</jats:italic> < 0.001), more than doubling the risk among individuals with MBL alone (HR = 3.30; 95% CI: 2.06–5.30; <jats:italic>P</jats:italic> < 0.001). In contrast, the risk associated with CHIP alone was attenuated and no longer statistically significant (HR = 1.63; 95% CI: 0.77–3.47; <jats:italic>P</jats:italic> = 0.20). MBL and CHIP are independent hematological precursor conditions. While their combined presence amplifies the risk of lymphoid malignancy, CHIP alone may not be a strong independent risk factor.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"3 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145447376","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 : 2025-11-05DOI: 10.1038/s41408-025-01372-z
Julie Bruneau, Sophie Georgin-Lavialle, Sophia Ladraa, Zakia Belaid, Isabelle Plo, Sébastien Letard, Erinn Soucie, Irena Draskovic, Nicolas Goudin, Marie Bouillié, Yves Lepelletier, Julien Rossignol, Laura Polivka, Laurent Frenzel, Olivier Lortholary, Sylvie Fraitag, Christine Bodemer, Patrick Revy, Michel Arock, Thierry-Jo Molina, Arturo Londono-Vallejo, Patrice Dubreuil, Leila Maouche-Chretien, Olivier Hermine
{"title":"Telomere occupancy by TRF2 is altered by KIT mutations and correlates with mastocytosis regression","authors":"Julie Bruneau, Sophie Georgin-Lavialle, Sophia Ladraa, Zakia Belaid, Isabelle Plo, Sébastien Letard, Erinn Soucie, Irena Draskovic, Nicolas Goudin, Marie Bouillié, Yves Lepelletier, Julien Rossignol, Laura Polivka, Laurent Frenzel, Olivier Lortholary, Sylvie Fraitag, Christine Bodemer, Patrick Revy, Michel Arock, Thierry-Jo Molina, Arturo Londono-Vallejo, Patrice Dubreuil, Leila Maouche-Chretien, Olivier Hermine","doi":"10.1038/s41408-025-01372-z","DOIUrl":"https://doi.org/10.1038/s41408-025-01372-z","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"166 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440876","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 : 2025-11-05DOI: 10.1038/s41408-025-01408-4
Kyle L Yu,Matthew Ho,Luca Paruzzo,Federico Stella,Heta Patel,Zainul S Hasanali,Shivani Kapur,Adam J Waxman,Dan T Vogl,Edward A Stadtmauer,Joseph A Fraietta,Marco Ruella,Adam D Cohen,Alfred L Garfall,Sandra Susanibar-Adaniya
{"title":"Outcomes of relapse after teclistamab therapy in multiple myeloma.","authors":"Kyle L Yu,Matthew Ho,Luca Paruzzo,Federico Stella,Heta Patel,Zainul S Hasanali,Shivani Kapur,Adam J Waxman,Dan T Vogl,Edward A Stadtmauer,Joseph A Fraietta,Marco Ruella,Adam D Cohen,Alfred L Garfall,Sandra Susanibar-Adaniya","doi":"10.1038/s41408-025-01408-4","DOIUrl":"https://doi.org/10.1038/s41408-025-01408-4","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"90 1","pages":"193"},"PeriodicalIF":12.8,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440601","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 : 2025-11-04DOI: 10.1038/s41408-025-01405-7
Jerry Janssen, Zhen Li, Thera A. M. Wormhoudt, Anna Beentjes, Harutai Nimaris, Kok P. M. van Kessel, C. Ellen van der Schoot, Arnon P. Kater, Anton W. Langerak, Ten Feizi, Jeroen E. J. Guikema, Richard J. Bende, Carel J. M. van Noesel
{"title":"Chronic lymphocytic leukemia specificity analyses unveil bacterial lipopolysaccharides as the cognate ligands of established stereotyped BCR subsets","authors":"Jerry Janssen, Zhen Li, Thera A. M. Wormhoudt, Anna Beentjes, Harutai Nimaris, Kok P. M. van Kessel, C. Ellen van der Schoot, Arnon P. Kater, Anton W. Langerak, Ten Feizi, Jeroen E. J. Guikema, Richard J. Bende, Carel J. M. van Noesel","doi":"10.1038/s41408-025-01405-7","DOIUrl":"https://doi.org/10.1038/s41408-025-01405-7","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"69 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145434405","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 : 2025-11-04DOI: 10.1038/s41408-025-01406-6
Luis E Aguirre,Richard M Stone,Daniel J DeAngelo,Maximilian Stahl
{"title":"Correspondence on: Oral decitabine cedazuridine with and without venetoclax in higher-risk myelodysplastic syndromes or chronic myelomonocytic leukemia: a propensity score-matched study.","authors":"Luis E Aguirre,Richard M Stone,Daniel J DeAngelo,Maximilian Stahl","doi":"10.1038/s41408-025-01406-6","DOIUrl":"https://doi.org/10.1038/s41408-025-01406-6","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"1 1","pages":"192"},"PeriodicalIF":12.8,"publicationDate":"2025-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145440603","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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