Blood最新文献

{"title":"How I Treat Plasma Cell Leukemia.","authors":"Samer Al Hadidi, Frits van Rhee, Larry D Anderson","doi":"10.1182/blood.2025032145","DOIUrl":"https://doi.org/10.1182/blood.2025032145","url":null,"abstract":"<p><p>Plasma cell leukemia (PCL) represents an exceptionally aggressive plasma cell malignancy defined by ≥5% circulating plasma cells in peripheral blood of patients otherwise meeting diagnostic criteria for multiple myeloma (MM), per International Myeloma Working Group consensus. This ultra-high-risk disease exhibits distinctive clinical features including frequent extramedullary involvement, severe cytopenias, hypercalcemia, renal insufficiency, and/or significantly elevated β2-microglobulin and lactate dehydrogenase levels. The molecular landscape includes high-risk cytogenetic abnormalities and mutations that promote accelerated proliferation, apoptotic resistance, immune evasion, and bone marrow microenvironmental independence through dysregulated adhesion molecule and chemokine receptor expression. While autologous stem cell transplantation, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies improved historical outcomes, the therapeutic paradigm continues to evolve. Novel therapeutic approaches including B-cell maturation antigen (BCMA)-directed therapies (bispecific antibodies and chimeric antigen receptor T-cell therapy), GPRC5D-targeted therapy, and BCL-2 inhibition demonstrate promise in treating both primary and secondary PCL. Despite these advances, PCL remains inadequately studied, with treatment approaches predominantly extrapolated from MM trials where PCL patients have largely been excluded. This review synthesizes current evidence and presents illustrative clinical cases demonstrating practical treatment approaches, while highlighting critical knowledge gaps requiring dedicated prospective clinical trials to meaningfully improve outcomes in this challenging disease entity.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":""},"PeriodicalIF":23.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147810996","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":"Nuclear architecture: a mechanical lever for HSC fitness.","authors":"Rasha Rezk","doi":"10.1182/blood.2026033532","DOIUrl":"https://doi.org/10.1182/blood.2026033532","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"147 18","pages":"2023-2024"},"PeriodicalIF":23.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761909","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":"Dissecting the genetic threads underlying the fabric of pediatric myelofibrosis.","authors":"Zubaidah Al-Jumaili, Xenia Parisi","doi":"10.1182/blood.2025032708","DOIUrl":"https://doi.org/10.1182/blood.2025032708","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"147 18","pages":"2156"},"PeriodicalIF":23.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761498","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":"Plasmodium knowlesi can adapt to infect Duffy-negative erythrocytes.","authors":"Maria Zinga, Amy Ibrahim, Franziska Mohring, Sittinont Chainarin, Thorey K Jonsdottir, Sutharinee Ngernna, Brian Amabilino-Perez, Tossapol Pholcharee, Anna Turkiewicz, Susana Campino, Taane G Clark, Jun Miao, Liwang Cui, Wanlapa Roobsoong, Jetsumon Sattabongkot, Robert W Moon, Wang Nguitragool","doi":"10.1182/blood.2025029557","DOIUrl":"10.1182/blood.2025029557","url":null,"abstract":"<p><strong>Abstract: </strong>Plasmodium knowlesi, a zoonotic malaria species, has become a significant public health concern in Southeast Asia. In regions such as Malaysia and southern Thailand, P knowlesi incidence has risen, even as other human malaria parasites are nearing elimination. Similar to its close relative Plasmodium vivax, P knowlesi relies on the Duffy antigen receptor for chemokine (DARC) as a key receptor for erythrocyte invasion. Only Duffy-positive individuals are thought to be susceptible to clinical infection. Here, we demonstrate that P knowlesi possesses greater invasion plasticity than previously recognized. This parasite can bypass the need for DARC, as shown by its in vitro adaptation to invade and replicate within Duffy-negative (Fy-) erythrocytes. This adaptation is stable and independent of DARC binding, enabling the adapted parasite line to be maintained in Fy- erythrocytes and to resist inhibition by α-DARC antibodies. Genomic analysis identified a genomic recombination event between the parasite's dbpα and dbpγ genes, resulting in a new chimeric gene dbpαγ. Using CRISPR-Cas9 targeted reversion, we could demonstrate that dbpαγ is essential for invasion of Fy- erythrocytes. These findings shed new light on the invasion plasticity of P knowlesi, with implications for the parasite's potential spread beyond Southeast Asia and for understanding the complex host-cell specificity and atypical invasion pathways seen in P vivax.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2132-2142"},"PeriodicalIF":23.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146212139","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 randomized phase 2 study of ipilimumab, nivolumab, and brentuximab vedotin in patients with relapsed Hodgkin lymphoma.","authors":"Catherine S Diefenbach, Opeyemi Jegede, Victoria Wang, Stephen M Ansell, Lale Kostakoglu, Christian Steidl, Yasodha Natkunam, David W Scott, Richard F Ambinder, Kevin A David, Ranjana H Advani, Nancy L Bartlett, Michael J Robertson, Sachdev P Thomas, Jonathon Cohen, Sami Ibrahimi, Gaurav Goyal, Neha Mehta-Shah, Jennifer E Amengual, Christopher J Forlenza, Peter D Cole, Fenghai Duan, Kara Kelly, Brad S Kahl","doi":"10.1182/blood.2025029546","DOIUrl":"10.1182/blood.2025029546","url":null,"abstract":"<p><strong>Abstract: </strong>The phase 1/2 Intergroup study E4412 investigated checkpoint blockade with nivolumab (Nivo) and ipilimumab (Ipi) combined with the CD30 targeting antibody-drug conjugate brentuximab vedotin (BV) in relapsed/refractory classic Hodgkin lymphoma. A total of 147 patients aged ≥12 years were randomized between BV/Nivo and BV/Ipi/Nivo; 132 patients were included in the primary efficacy analysis. The complete response (CR) rate, was 64.7% (52.2, 75.9) for BV/Nivo and 70.3% (57.6, 81.1) for BV/Ipi/Nivo (1-sided P = .29). The median survival follow-up was 38.0 months (interquartile range, 32.6-48.1). Progression-free survival (PFS) did not significantly differ between the 2 arms (hazard ratio [HR], 0.78, confidence interval [CI], 0.39-1.57; 1-sided P = .24). Treatment-related grade 3+ toxicities in the adult cohort, excluding rash, were similar between both arms (38.5% BV/Nivo and 39.3% BV/Ipi/Nivo); there was a higher frequency of grade 3 rash with BV/Ipi/Nivo (24.6%) compared with BV/Nivo (9.2%). We compared PFS by stem cell transplantation (SCT) status in a planned before hoc comparison; 58 patients received SCT, and 36-month PFS (from SCT) was >90% for both arms. Sixty-six patients were progression free after the first scan and did not undergo SCT. The 36-month PFS was 73.0% (54.5, 85.0) for BV/Ipi/Nivo compared with 45.8% (26.3, 63.4) for BV/Nivo (HR, 0.45; CI, 0.19-1.08; 1-sided P = .03). The study did not meet its primary end point of superior CR rate for the triplet, but it supports the use of checkpoint antibody-drug conjugate induction prior to auto SCT, and there is an intriguing signal of disease control for patients wishing to defer or avoid SCT with the triplet of BV/Ipi/Nivo. This trial was registered at www.clinicaltrials.gov as NCT01896999.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2041-2052"},"PeriodicalIF":23.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149004","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":"Plasmin tames lung inflammation by redirecting immune cells.","authors":"Rick Kapur","doi":"10.1182/blood.2025032938","DOIUrl":"https://doi.org/10.1182/blood.2025032938","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"147 18","pages":"2026-2028"},"PeriodicalIF":23.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761876","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":"Plasmodium gets inside through the back door.","authors":"Ryan P Jajosky, Sean R Stowell","doi":"10.1182/blood.2026033250","DOIUrl":"https://doi.org/10.1182/blood.2026033250","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"147 18","pages":"2030-2032"},"PeriodicalIF":23.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147762020","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":"Checkpoint blockade in HL: is transplant still needed?","authors":"Andy I Chen","doi":"10.1182/blood.2026033265","DOIUrl":"10.1182/blood.2026033265","url":null,"abstract":"","PeriodicalId":9102,"journal":{"name":"Blood","volume":"147 18","pages":"2021-2022"},"PeriodicalIF":23.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760697","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":"Nucleoplasmic ZNF467 condensates boost hematopoietic stem cell engraftment via ICAM1-mediated mechanical reprogramming.","authors":"Yandan Chen, Jinghao Shen, Zaisheng Lin, Qingwei Ding, Xiashiyao Zhang, Meng Zhang, Haoxiang Yang, Han Yao, Sheng Liu, Jun Wan, Shize Liu, Xiaopeng Jia, Xiaodong Wang, Uet Yu, Siguo Hao, Muqing Cao, Hongyuan Jiang, Bin Guo","doi":"10.1182/blood.2025031247","DOIUrl":"10.1182/blood.2025031247","url":null,"abstract":"<p><strong>Abstract: </strong>Hematopoietic stem cell (HSC) transplantation is a life-saving therapy for immune deficiencies and hematologic malignancies, but its efficacy is limited by poor engraftment. Therapeutic enhancement of HSC grafts requires deeper insight into the intrinsic determinants of their regenerative capacity. Here, we identify mechanical robustness as a critical feature distinguishing human HSCs from multipotent progenitors (MPPs). Through integrative biomechanical and transcriptomic profiling, we reveal that ZNF467 is a key regulator of HSC mechanical integrity. Loss of ZNF467 disrupts HSC mechanical fitness and abolishes long-term engraftment. Conversely, an engineered phase-separating ZNF467 variant enhanced mechanical strength and engraftment by activating a mechanoresponsive transcriptional program, including upregulation of ICAM1. ICAM1+ hematopoietic stem and progenitor cells exhibit superior biomechanical properties and improved engraftment efficiency. Furthermore, the phase-separation activity of nucleoplasmic ZNF467 (npZNF467) is crucial for its mechanical reprogramming function, and ectopic npZNF467 expression enhances the engraftment capacity of MPPs. Our findings establish biomechanical regulation as an important determinant of stem cell identity and reveal new strategies for engineering stem cells with enhanced regenerative capacity.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2064-2080"},"PeriodicalIF":23.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164127","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":"Silencing of PAI-1 using siRNA-lipid nanoparticles reduces thrombosis and prolongs life span in murine models.","authors":"Francesca Ferraresso, Chad W Skaer, Zimu Wei, Woosuk S Hur, Hongyin Yu, Monica Seadler, Taylor H Y Chen, Wen Dai, Manoj Paul, Catherine Lapointe, Laura M Ketelboeter, Hayley Lund, Geoffrey G Rodriguez, Lih Jiin Juang, Amy W Strilchuk, Youjie Zhang, Pieter R Cullis, Mitchell R Dyer, Allison L Gerras, Qizhen Shi, James P Luyendyk, Matthew J Flick, Ze Zheng, Christian J Kastrup","doi":"10.1182/blood.2025029834","DOIUrl":"10.1182/blood.2025029834","url":null,"abstract":"<p><strong>Abstract: </strong>Plasminogen activator inhibitor 1 (PAI-1) is an inhibitor of fibrinolysis, thereby promoting blood clot stabilization. PAI-1 contributes to thrombosis, diet-induced obesity, and age-associated diseases, such as diabetes, cancer, and Alzheimer disease. Circulating PAI-1 level increases with age, contributing to the increased thrombotic risk in age-related diseases. In contrast, partial PAI-1 deficiency protects patients from cardiovascular morbidity and extends life span. Decreasing circulating PAI-1 levels has both experimental and therapeutic value. RNA gene therapy can regulate the levels of target proteins, including those not amenable to traditional small-molecule or antibody-based therapies. Here, we developed a therapeutic approach to induce long-lasting PAI-1 knockdown in vivo with small interfering RNA (siRNA)-lipid nanoparticles (siPAI-1). One dose of siPAI-1 resulted in 90% knockdown of plasma PAI-1 and lasted 10 days after administration with no overt toxicity. siPAI-1 decreased thrombus weight after complete ligation of the inferior vena cava (IVC) in young and aged mice and increased survival in aged mice 4 days post-IVC ligation. Hepatic PAI-1 mRNA expression in diet-induced obese mice was >10 times higher than in healthy mice and was exponentially correlated with body weight. One dose of siPAI-1 in obese mice resulted in 70% knockdown of circulating PAI-1. Furthermore, siPAI-1 normalized the supraphysiologic concentration of PAI-1 in aged mice and prolonged life span in a fast-aging mouse model. Thus, siRNA-mediated PAI-1 knockdown represents a long-term antithrombotic approach and effective strategy to limit pathologic impact of PAI-1 in aging and age-related diseases.</p>","PeriodicalId":9102,"journal":{"name":"Blood","volume":" ","pages":"2053-2063"},"PeriodicalIF":23.1,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12994142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146050360","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}