Pub Date : 2025-10-24DOI: 10.1038/s41408-025-01371-0
Elena Alejo,Verónica González-Calle,Patricia Blázquez,Borja Puertas,Cristina Agulló,Beatriz Rey-Búa,Norma C Gutiérrez,Noemi Puig,María-Victoria Mateos
Recent studies have advanced the understanding of the pathogenesis of monoclonal gammopathy of uncertain significance (MGUS), describing the influence of a proinflammatory bone marrow environment on the risk of progression. While albumin is a known inflammatory prognostic biomarker in multiple myeloma, its role in MGUS has not been explored. We conducted a retrospective study to investigate the prognostic value of albumin in MGUS. Eight hundred and thirty-eight patients with MGUS were included: 71 (8.5%) presented hypoalbuminemia (≤3.5 g/dL) at diagnosis. Hypoalbuminemia was more common in men (63.4% vs. 49.3%; P = 0.025), older age (≥70 years: 74.6% vs. 57.2%; P = 0.005), and IgA isotype (33.8% vs. 21.4%; P = 0.018). These patients presented lower hemoglobin levels and higher creatinine values (P < 0.001 and P < 0.001). Serum M protein ≥ 1.5 g/dL (HR 18.9 [95% CI, 1.8-200.8]; P = 0.015) and hypoalbuminemia (HR 14.7 [95% CI, 1.7-124.7]; P = 0.014) were identified as independent prognostic factors for progression. In our series, Mayo Clinic and MGUS-like phenotype models were validated, and the incorporation of hypoalbuminemia into these models helped identify a subgroup of intermediate-risk patients with a higher risk of progression. In conclusion, if confirmed by independent studies, hypoalbuminemia could be integrated into existing prognostic models, improving risk stratification and guiding clinical decision-making.
{"title":"Hypoalbuminemia: a new risk factor for progression in patients with monoclonal gammopathy of uncertain significance.","authors":"Elena Alejo,Verónica González-Calle,Patricia Blázquez,Borja Puertas,Cristina Agulló,Beatriz Rey-Búa,Norma C Gutiérrez,Noemi Puig,María-Victoria Mateos","doi":"10.1038/s41408-025-01371-0","DOIUrl":"https://doi.org/10.1038/s41408-025-01371-0","url":null,"abstract":"Recent studies have advanced the understanding of the pathogenesis of monoclonal gammopathy of uncertain significance (MGUS), describing the influence of a proinflammatory bone marrow environment on the risk of progression. While albumin is a known inflammatory prognostic biomarker in multiple myeloma, its role in MGUS has not been explored. We conducted a retrospective study to investigate the prognostic value of albumin in MGUS. Eight hundred and thirty-eight patients with MGUS were included: 71 (8.5%) presented hypoalbuminemia (≤3.5 g/dL) at diagnosis. Hypoalbuminemia was more common in men (63.4% vs. 49.3%; P = 0.025), older age (≥70 years: 74.6% vs. 57.2%; P = 0.005), and IgA isotype (33.8% vs. 21.4%; P = 0.018). These patients presented lower hemoglobin levels and higher creatinine values (P < 0.001 and P < 0.001). Serum M protein ≥ 1.5 g/dL (HR 18.9 [95% CI, 1.8-200.8]; P = 0.015) and hypoalbuminemia (HR 14.7 [95% CI, 1.7-124.7]; P = 0.014) were identified as independent prognostic factors for progression. In our series, Mayo Clinic and MGUS-like phenotype models were validated, and the incorporation of hypoalbuminemia into these models helped identify a subgroup of intermediate-risk patients with a higher risk of progression. In conclusion, if confirmed by independent studies, hypoalbuminemia could be integrated into existing prognostic models, improving risk stratification and guiding clinical decision-making.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"131 1","pages":"179"},"PeriodicalIF":12.8,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357903","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 : 2025-10-24DOI: 10.1038/s41408-025-01370-1
Weijun Zhou,Jinyi Yu,Fuyu Li,Yuting Huang,Jingwen Du,Anqin Wu,Kankan Wang
Accumulation of genetic mutations in malignant myeloid precursor cells leads to an extremely poor prognosis for patients with acute myeloid leukemia (AML). Immunogenic neoantigens recognized by T cell receptor (TCR) can elicit effective immune responses against malignant cells with corresponding somatic mutations. To broaden the range of targeted treatments for AML, in this study, we explored the feasibility of immunotherapy targeting neoantigens arising from recurrent mutations, which are exclusively present on leukemic cells. We used data-driven methods to select seven neoantigens from four frequently mutated genes (NPM1, FLT3, TP53, and DNMT3A) associated with HLA-A*02:01-positive AML patients. Functional assays demonstrated that neoantigens derived from NPM1/W288fs, FLT3/D835H, and FLT3/D835Y were shown to induce specific T cell responses in AML patients. We further identified the specific TCR sequences from healthy donors capable of recognizing these neoantigens. In-depth studies of their specific T cells revealed the presence of dominant αβTCRs that could specifically recognize NPM1/W288fs and FLT3/D835H in an HLA-A*02:01-restricted manner. T cells engineered with each αβTCR selectively recognized and killed HLA-A*02:01-positive AML targets endogenously expressing corresponding mutations. Overall, our findings support the clinical translation of adoptive neoantigen-specific TCR-engineered T cells as a novel therapeutic strategy for treating AML.
{"title":"Identification of specific T-cell response and T-cell receptor targeting shared neoantigen for acute myeloid leukemia.","authors":"Weijun Zhou,Jinyi Yu,Fuyu Li,Yuting Huang,Jingwen Du,Anqin Wu,Kankan Wang","doi":"10.1038/s41408-025-01370-1","DOIUrl":"https://doi.org/10.1038/s41408-025-01370-1","url":null,"abstract":"Accumulation of genetic mutations in malignant myeloid precursor cells leads to an extremely poor prognosis for patients with acute myeloid leukemia (AML). Immunogenic neoantigens recognized by T cell receptor (TCR) can elicit effective immune responses against malignant cells with corresponding somatic mutations. To broaden the range of targeted treatments for AML, in this study, we explored the feasibility of immunotherapy targeting neoantigens arising from recurrent mutations, which are exclusively present on leukemic cells. We used data-driven methods to select seven neoantigens from four frequently mutated genes (NPM1, FLT3, TP53, and DNMT3A) associated with HLA-A*02:01-positive AML patients. Functional assays demonstrated that neoantigens derived from NPM1/W288fs, FLT3/D835H, and FLT3/D835Y were shown to induce specific T cell responses in AML patients. We further identified the specific TCR sequences from healthy donors capable of recognizing these neoantigens. In-depth studies of their specific T cells revealed the presence of dominant αβTCRs that could specifically recognize NPM1/W288fs and FLT3/D835H in an HLA-A*02:01-restricted manner. T cells engineered with each αβTCR selectively recognized and killed HLA-A*02:01-positive AML targets endogenously expressing corresponding mutations. Overall, our findings support the clinical translation of adoptive neoantigen-specific TCR-engineered T cells as a novel therapeutic strategy for treating AML.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"4 1","pages":"178"},"PeriodicalIF":12.8,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145357902","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 : 2025-10-22DOI: 10.1038/s41408-025-01396-5
Sonja Wurm,Jennifer M Moritz,Verena Petzer,Dominik Wolf,Karoline V Gleixner,Wolfgang R Sperr,Christina Groiss,Sigrid Machherndl-Spandl,Gregor Eisenwort,Elisabeth Koller,Johannes Schoeche,Clemens Petrasch,Josef Singer,Daniel M Mayer,Gudrun Pregartner,Annkristin Heine,Albert Wölfler,Heinz Sill,Andreas Reinisch,Armin Zebisch
{"title":"Efficacy assessment following shortened venetoclax exposure in AML patients treated with venetoclax plus hypomethylating agents: a real-world, multicentric study.","authors":"Sonja Wurm,Jennifer M Moritz,Verena Petzer,Dominik Wolf,Karoline V Gleixner,Wolfgang R Sperr,Christina Groiss,Sigrid Machherndl-Spandl,Gregor Eisenwort,Elisabeth Koller,Johannes Schoeche,Clemens Petrasch,Josef Singer,Daniel M Mayer,Gudrun Pregartner,Annkristin Heine,Albert Wölfler,Heinz Sill,Andreas Reinisch,Armin Zebisch","doi":"10.1038/s41408-025-01396-5","DOIUrl":"https://doi.org/10.1038/s41408-025-01396-5","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"43 1","pages":"175"},"PeriodicalIF":12.8,"publicationDate":"2025-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145339337","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 : 2025-10-21DOI: 10.1038/s41408-025-01378-7
Dogan Yildiz,Ahmet Emre Eskazan
{"title":"STAMP inhibitors and their future in CML therapy: a critical analysis.","authors":"Dogan Yildiz,Ahmet Emre Eskazan","doi":"10.1038/s41408-025-01378-7","DOIUrl":"https://doi.org/10.1038/s41408-025-01378-7","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"15 1","pages":"173"},"PeriodicalIF":12.8,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338609","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 : 2025-10-21DOI: 10.1038/s41408-025-01369-8
Efstathios Kastritis, Panagiotis Malandrakis, Ioannis V Kostopoulos, Ioannis Ntanasis-Stathopoulos, Irene Solia, Foteini Theodorakakou, Vasiliki Spiliopoulou, Despina Fotiou, Magdalini Migkou, Nikolaos Kanellias, Evangelos Eleutherakis-Papaiakovou, Konstantina Taouxi, Alexandra Papadimou, Christine-Ivy Liacos, Maria Gavriatopoulou, Ourania Tsitsilonis, Evangelos Terpos, Meletios-Athanasios Dimopoulos
{"title":"Circulating tumor cells by Next Generation Flow Cytometry as a new prognostic biomarker for patients with asymptomatic monoclonal gammopathies.","authors":"Efstathios Kastritis, Panagiotis Malandrakis, Ioannis V Kostopoulos, Ioannis Ntanasis-Stathopoulos, Irene Solia, Foteini Theodorakakou, Vasiliki Spiliopoulou, Despina Fotiou, Magdalini Migkou, Nikolaos Kanellias, Evangelos Eleutherakis-Papaiakovou, Konstantina Taouxi, Alexandra Papadimou, Christine-Ivy Liacos, Maria Gavriatopoulou, Ourania Tsitsilonis, Evangelos Terpos, Meletios-Athanasios Dimopoulos","doi":"10.1038/s41408-025-01369-8","DOIUrl":"10.1038/s41408-025-01369-8","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"15 1","pages":"170"},"PeriodicalIF":11.6,"publicationDate":"2025-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12540748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145343086","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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