Blood最新文献

{"title":"A rare phenotype of peripheral T-cell lymphoma, NOS: coexpression of CD15, CD20, and T follicular helper markers in a DUSP22alt case.","authors":"Muna Al Jabri,Ali Sakhdari","doi":"10.1182/blood.2025028986","DOIUrl":"https://doi.org/10.1182/blood.2025028986","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"71 6 1","pages":"260"},"PeriodicalIF":20.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594038","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}

{"title":"Loss of DCAF8 impairs hematopoietic stem cell function with cellular senescence via the DOCK11-CDC42 axis.","authors":"Pengfei Xu,Xiuli Zhang,Donghe Li,Bo Jiao,Jiawei Nie,Yi Huang,Zhizhou Xia,Jiaoyang Li,Yuqing Dan,Xu Huang,Lei Yan,Rui Zhang,Wei Huang,Xinru Wang,Shiyu Ji,Yong Cang,Ruibao Ren,Ping Liu","doi":"10.1182/blood.2024027335","DOIUrl":"https://doi.org/10.1182/blood.2024027335","url":null,"abstract":"Hematopoietic stem cells (HSCs) are responsible for sustaining hematopoietic system throughout life, and their functional decline contributes to hematological disorders and organismal aging. Understanding the molecular mechanisms that govern HSC function is critical for developing interventions for treating and preventing aging-related diseases. Here, we show that DCAF8, a substrate recognition component of Cullin-RING E3 ubiquitin ligases, is highly expressed in HSCs and undergoes a progressive decline with age. Loss of DCAF8 in mice results in impaired function in HSCs, characterized by increased number yet decreased self-renewal capacity, which associates with cellular senescence and elevated DNA damage. Mechanistically, DCAF8 mediates the degradation of DOCK11, a guanine nucleotide exchange factor for CDC42. In the absence of DCAF8, DOCK11 accumulates, leading to elevated CDC42 activity and consequential loss of polarity of HSCs. Knocking out Dock11 mitigates the senescence, DNA damage, and self-renewal defects of Dcaf8-/- HSCs. This study highlights a critical role of DCAF8 in preventing HSC senescence via the DOCK11-CDC42 axis and suggests potential therapeutic targets for preventing functional decline in HSCs.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"22 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603914","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}

{"title":"Beware the zombie enzyme.","authors":"David Dominguez-Sola","doi":"10.1182/blood.2025028953","DOIUrl":"https://doi.org/10.1182/blood.2025028953","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"146 2","pages":"135-136"},"PeriodicalIF":21.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599418","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}

{"title":"Silence of the myeloma clones: GPRC5D epigenetic regulation.","authors":"Holly Lee,Nizar J Bahlis","doi":"10.1182/blood.2025028865","DOIUrl":"https://doi.org/10.1182/blood.2025028865","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"4 1","pages":"133-135"},"PeriodicalIF":20.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594041","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}

{"title":"The neutrophil antigen 3a/b polymorphism in SLC44A2 unexpectedly encodes the Csa/Csb red cell antigens.","authors":"Romain Duval, Alissa Soudry, Jonathan De Oliveira Rios, Sarah Liane Linguet, Miguel Taillepierre, Graziella Matesic, Alexandre Raneri, Guy Laiguillon, Emilie Le Toriellec, Emilie-Fleur Gautier, Damien Vainqueur, Jérôme Babinet, Cécile Masson, Jean Christophe Gelly, Caroline Le Van Kim, Marc Romana, Dawei Chen, Sentot Santoso, Berengere Koehl, Thierry Peyrard, Slim Azouzi","doi":"10.1182/blood.2024026285","DOIUrl":"10.1182/blood.2024026285","url":null,"abstract":"<p><strong>Abstract: </strong>The Csa blood group antigen was identified >50 years ago, but its genetic basis has yet to be elucidated. All our recent genomic investigation has failed to resolve the genetic basis of this enigmatic antigen. By investigating the association of the human neutrophil antigen (HNA)-3a/b polymorphism (rs2288904-G/A) in SLC44A2 with clinical features of sickle cell disease, we incidentally discovered that rare subjects with the homozygous HNA-3b/b genotype also carry the uncommon Cs(a-) phenotype. We genotyped this single-nucleotide polymorphism in a cohort of 25 Cs(a-) subjects and found that all of them showed an HNA-3b/b genotype. This result suggests that the high-prevalence allele with rs2288904 (HNA-3a; 455G) encoding Arg152 encodes the high-prevalence Csa. Accordingly, anti-Csa does not react with solute carrier (SLC)44A2null red blood cells (RBCs), SLC44A2 knockout K562 cells, and K562 cells expressing HNA-3b, confirming that the Csa and Csb antigens are carried on this protein. Furthermore, mass spectrometry analysis of SLC44A2 from neutrophils and RBCs, along with serological investigation, showed that, despite HNA-3a and Csa having the same genetic basis, anti-HNA-3a and anti-Csa recognize different epitopes on the SLC44A2 protein. Overall, our data resolve the genetic bases of the Cs(a-) and Cs(b-) blood phenotypes, with new insights on the anti-HNA-3a specificity.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"247-253"},"PeriodicalIF":21.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639669","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}

{"title":"Real-world data provide a CARbon copy for ide-cel.","authors":"Timothy Schmidt","doi":"10.1182/blood.2025029274","DOIUrl":"https://doi.org/10.1182/blood.2025029274","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"693 1","pages":"131-133"},"PeriodicalIF":20.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594040","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}

{"title":"A noncoding mutation in the NOTCH1 gene initiates oncogenic NOTCH signaling via wild-type NICD stabilization in CLL.","authors":"Min Guo,Tugba Memis,Alena Sophie Ehrmann,Anselm Pittrof,Bernd Baumann,Francesca Ferrante,Eugen Tausch,Kirsten Fischer,Hartmut Döhner,Tilman Borggrefe,Stephan Stilgenbauer,Ulrich Pannicke,Klaus Schwarz,Daniel Mertens,Franz Oswald","doi":"10.1182/blood.2025028529","DOIUrl":"https://doi.org/10.1182/blood.2025028529","url":null,"abstract":"Chronic Lymphocytic Leukemia (CLL) is the most common chronic blood cancer in adults. Active NOTCH signaling in CLL is associated with poorer prognosis. Importantly, CLL patients with NOTCH1 non-coding mutations in the 3-prime untranslated region (3'UTR) manifested with a more aggressive disease course even compared to those with mutations in the NOTCH1 coding region. Here, we comprehensively characterize a cryptic splice acceptor site in 3'UTR of the NOTCH1 gene being converted into a stronger site. The functional consequences of the resulting NOTCH1 protein variants depend on the exact localization of the splice site, the used open reading frame and the appearance of the next STOP codon. The most frequent 3'UTR mutation (g.139390152, A>G) generates a novel NOTCH1 protein, lacking the PEST domain but expressing an altered C-terminus consisting of 68 amino acids. Mechanistically, we show that this splice variant (NOTCH1 152) is transcriptionally less active and dysregulates the regular ubiquitination dependent degradation of the wild type NOTCH1 intracellular domain (NICD) in trans. Thus, the NOTCH1 152 variant acts as a \"sponge\" protein in a novel mechanism of oncogenic NOTCH signaling activation, explaining the detrimental disease outcome of CLL patients with non-coding NOTCH1 mutations. We propose that the detection of NOTCH1 152 protein by specific antibodies is a useful prognostic marker for CLL patients.","PeriodicalId":9102,"journal":{"name":"Blood","volume":"12 1","pages":""},"PeriodicalIF":20.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603963","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}

{"title":"Iron overload impacts TCR γδ cell immunity.","authors":"José Pedro Loureiro,M Fátima Macedo","doi":"10.1182/blood.2025029261","DOIUrl":"https://doi.org/10.1182/blood.2025029261","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"22 1","pages":"139-140"},"PeriodicalIF":20.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594042","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}

{"title":"Standard-of-care idecabtagene vicleucel for relapsed/refractory multiple myeloma.","authors":"Surbhi Sidana, Nausheen Ahmed, Othman Salim Akhtar, Ruta Brazauskas, Temitope Oloyede, Matthew Bye, Doris Hansen, Christopher Ferreri, Ciara L Freeman, Aimaz Afrough, Larry D Anderson, Binod Dhakal, Devender Dhanda, Lohith Gowda, Hamza Hashmi, Melanie J Harrison, Amani Kitali, Heather Landau, Abu-Sayeef Mirza, Pallavi Patwardhan, Muzaffar Qazilbash, Saad Usmani, Krina Patel, Taiga Nishihori, Siddhartha Ganguly, Marcelo C Pasquini","doi":"10.1182/blood.2024026216","DOIUrl":"10.1182/blood.2024026216","url":null,"abstract":"<p><strong>Abstract: </strong>Idecabtagene vicleucel (ide-cel) was the first US Food and Drug Administration-approved chimeric antigen receptor T-cell (CAR-T) therapy for multiple myeloma (MM). However, because clinical trials are highly selective with stringent eligibility criteria, the objective of this study was to evaluate the safety and effectiveness of standard-of-care (SOC) ide-cel in the real world. Using the Center for International Blood and Marrow Transplant Research registry, we evaluated 821 patients who received SOC ide-cel. Median follow-up was 11.6 months. Median age was 66 years, and the cohort included 31% patients aged ≥70 years, with 15% Black and 7% Hispanic, and 77% of patients with ≥1 significant comorbidity. The median number of prior lines of therapy was 7, 15% patients previously received B-cell maturation antigen-directed therapy, 17% had extramedullary disease, and 27% had high-risk cytogenetics. Overall response rate was 73%, and complete response rate was 25%. Median progression-free survival was 8.8 months. Treatment-related mortality was reported in 6% of patients. Cytokine release syndrome was diagnosed in 80% of patients (grade ≥3, 3%). Immune effector cell-associated neurotoxicity syndrome was observed in 28% (grade ≥3, 5%), with no cases of Parkinsonism reported. Clinically significant infections were seen in 45% of patients. Second primary malignancies were reported in 4%, including 1% myeloid malignancies. This is, to our knowledge, the largest real-world study of ide-cel CAR-T therapy in patients with relapsed/refractory (R/R) MM. We observed a favorable safety and efficacy profile that mirrors trial experience, even in the setting of significant comorbidities in 77% of patients, many of which would have made them ineligible for the registrational KarMMa clinical trial. This trial was registered at www.clinicaltrials.gov as #NCT03361748.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"167-177"},"PeriodicalIF":21.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143810464","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}

{"title":"Unveiling the truth: different names, same antigen.","authors":"Nelson H Tsuno,Daisuke Takahashi","doi":"10.1182/blood.2025028939","DOIUrl":"https://doi.org/10.1182/blood.2025028939","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"34 1","pages":"141-143"},"PeriodicalIF":20.3,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594036","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}