Haematologica最新文献

{"title":"PTPN11 mutations define a rare but highly adverse subset of myelodysplastic syndromes.","authors":"Alexandre Bazinet,Alex Bataller,Guillermo Montalban-Bravo,Kelly Chien,Koji Sasaki,Wei Ying Jen,Mahesh Swaminathan,Tapan Kadia,Courtney DiNardo,Farhad Ravandi,Guillermo Garcia-Manero,Hagop Kantarjian","doi":"10.3324/haematol.2025.287874","DOIUrl":"https://doi.org/10.3324/haematol.2025.287874","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"48 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547737","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":"CD6 expression is an independent predictor of time to first treatment in chronic lymphocytic leukemia.","authors":"Laura Carrillo-Serradell,Juan Antonio Piñeyroa,Pablo Bousquets-Muñoz,Violeta Planells-Romeo,Lucía Aragón-Serrano,Sergi Casadó-Llombart,Dolors Colomer,María Velasco-de Andrés,Xose S Puente,Julio Delgado,Pablo Mozas,Francisco Lozano","doi":"10.3324/haematol.2025.287564","DOIUrl":"https://doi.org/10.3324/haematol.2025.287564","url":null,"abstract":"CD6 is a lymphocytic receptor expressed by all T cells and a subset of B and NK cells. It physically associates with the antigen-specific clonotypic receptor of T (TCR) cells, where it modulates the activation and differentiation signals delivered along lymphocyte development and upon peripheral antigen recognition. CD6 is also expressed in some B cell malignancies (e.g., chronic lymphocytic leukemia, CLL), though its biological role and clinical performance is largely unknown. To this end, we have evaluated the potential impact of CD6 differential expression in a CLL patient cohort. 270 CLL patient histories from the CLL-ES project with available RNA-Seq data have been analysed. High CD6 expression was found to be associated with mutated IGHV status and predictive of longer time to first treatment in a uni- and multivariable model (10-year probability of receiving treatment was 33 vs. 55 % in CD6hi and CD6lo groups, respectively, P = 0.0003) along with the lymphocyte count and the CLL International Prognostic Index. Further gene set enrichment analyses (GSEA) showed association of high CD6 expression with downregulation of MYC-regulated, mitotic spindle-related and RNA splicing-associated genes, all positively related to cancer progression. Interestingly, CD38, a widely studied adverse prognostic marker in CLL, was significantly downregulated in the CD6 high group, in agreement with flow cytometry data. These results reinforce the notion that CD6 may play a pivotal role in neoplastic B cell biology and lay the ground to further explore CD6 expression in the context of CLL prognoses.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"29 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547773","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":"Relapsed acute lymphoblastic leukemia: back to the drawing board.","authors":"Elad Jacoby","doi":"10.3324/haematol.2025.288191","DOIUrl":"https://doi.org/10.3324/haematol.2025.288191","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"29 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547764","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":"Safety and efficacyof the combination of copanlisib and nivolumab in patients with Richter's transformation or transformed non-Hodgkin lymphoma: results from a phase I trial.","authors":"Geoffrey Shouse,Canping Chen,Alexandra Muir,Leslie Popplewell,Tanya Siddiqi,Jasmine Zain,Alex F Herrera,Olga Danilova,Carly Roleder,Lili Wang,Stephen E F Spurgeon,Adam S Kittai,Lu Chen,Zheng Xia,Matthew S Davids,Alexey V Danilov","doi":"10.3324/haematol.2024.286945","DOIUrl":"https://doi.org/10.3324/haematol.2024.286945","url":null,"abstract":"Despite advances in targeted and cellular therapies, outcomes for patients with Richter's transformation (RT) and transformed non-Hodgkin lymphoma (tNHL) remain dismal. In this study we report safety and efficacy of the combination of the selective, small molecule inhibitor of phosphoinositide-3-kinase copanlisib, with the anti-PD-1 antibody nivolumab from a phase 1 multicenter investigator-sponsored study. Twenty-seven adult patients with relapsed and/or refractory RT or tNHL were treated with escalating doses of copanlisib IV on days 1, 8, and 15 (dose level [DL] 1-45 mg, DL2-60 mg) combined with nivolumab 240 mg IV on days 1 and 15 of a 28-day cycle. Three dose limiting toxicities occurred in 2 patients treated at DL2, hence 45 mg was determined the maximum tolerated dose and utilized in the expansion cohort. The most common treatment-related adverse events were diarrhea and anemia. All patients went off protocol, predominantly due to progressive disease and adverse events (67% and 26% of patients, respectively). Overall response rate (ORR) was 46%. Patients with transformed follicular lymphoma had ORR 67% (2 complete responses), with median progression free survival (PFS) 4.4 months (95% CI: 1.4-12.2). Patients with RT had ORR 31% (2 complete responses) with median PFS 2.0 months (95% CI: 0.7-4.9). Treatment resulted in downregulation of MYC and NFκB pathways in malignant B cells. Responding RT patients exhibited sustained activation of IFN-α and IFN-γ signaling pathways in CD4+ and CD8+ T cells. Overall, treatment with copanlisib and nivolumab demonstrated manageable toxicity and promising clinical efficacy in tNHL patients.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"20 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547733","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":"Aging-declined RNA exportation impairs hematopoietic stem cells by inducing R-loop.","authors":"Ruiqing Chen,Qiongye Dong,Lihong Zhou,Hanqing He,Yingxue Du,Qianwen Sun,Toshio Suda,Tao Cheng,Jianwei Wang","doi":"10.3324/haematol.2025.287765","DOIUrl":"https://doi.org/10.3324/haematol.2025.287765","url":null,"abstract":"Aging-related accumulation of DNA damage adversely affects hematopoietic stem cell (HSC). However, the mechanisms underlying this accumulation and strategies for its elimination to rejuvenate aged HSCs remain largely obscure. This study uncovers a notable surge in R-Loop presence within aged HSCs, notably co-localized with γH2AX and RPA (Replication Protein A), and correlated with RNA residency in the nucleus. Targeted induction of R-Loop impairs the function of HSCs. Mechanistically, RNA exportation is compromised in aged HSCs due to a decline in Alyref, the primary constituent of the TREX (transcription-export complex). Specifically, Alyref dysfunction results in RNA retention within the nucleus, mimicking the functional characteristics of aged HSCs. The nuclear accumulation of RNA leads to the formation of RNA:DNA hybrids, known as R-Loop structures, consequently inducing replication stress and DNA damage. Introducing a quantitative boost of Alyref in aged HSCs notably reinstates RNA transportation, diminishes R-Loop formation and replication stress, and ultimately enhances the performance of aged HSCs. Taken together, our research demonstrates the initial revelation that aging-triggered replication stress stems from abnormal RNA transportation-propelled R-Loop configurations, hinting at the potential of quantitatively modulating RNA transportation to mitigate the physiological drawbacks of aging on HSCs.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"71 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547765","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":"Mechanisms sensitive to different drugs mediate a pro-adhesive and pro-thrombotic platelet phenotype in anti-phospholipid syndrome.","authors":"Marina Camera,Marta Brambilla,Paola Adele Lonati,Alessia Becchetti,Claudia Grossi,Kevin Nallio,Arianna Da Via,Laura Trespidi,Maria Orietta Borghi,Francesco Tedesco,Pier Luigi Meroni","doi":"10.3324/haematol.2024.287133","DOIUrl":"https://doi.org/10.3324/haematol.2024.287133","url":null,"abstract":"Antiphospholipid antibodies (aPL) mediate platelet- and leukocyte-interaction with damaged endothelium, contributing to antiphospholipid syndrome (APS) vasculopathy. This study aimed to understand the mechanisms sustaining the pro-adhesive/-thrombotic platelet phenotype and the in vitro effects of different drugs. We included thirty-four primary APS (PAPS) patients and twelve healthy subjects (HS). All patients had medium/high aPL levels with vascular/obstetric symptoms according to the 2023 ACR/EULAR classification. In vivo, we evaluated by flow-cytometry platelet activation markers [P-selectin, activated GPIIbIIIa (aGPIIbIII)], Tissue Factor (TF), ApoER2 and β2GPI expression and plateletmonocyte and-granulocyte aggregates (PMA and PGA)]. In vitro, the impact of antiplatelet and anti-inflammatory drugs on platelet activation induced by different aPL subpopulations was investigated. PAPS patients exhibited greater percentages of circulating ApoER2pos-, P-selectinpos-, aGPIIbIIIapos-, TFpos-platelets, and TFpos-platelet-leukocyte aggregates. In vitro, HS blood incubation with PAPS plasma fully reproduced the activation found in vivo. While anti-β2GPI-Domain(D)1, but not anti- D4,5, IgG upregulated platelet TF expression only, the addition of IL-6 also induced P-Selectin and aGPIIbIIIa upregulation. An IL-6 receptor-blocking monoclonal antibody prevented the proadhesive/- coagulant platelet phenotype and the formation of platelet-leukocyte aggregates mediated by PAPS plasma or by total IgG plus exogenous IL-6. While aspirin and P2Y12 inhibitor fully inhibited platelet activation, hydroxychloroquine (HCQ) did not blunt TF expression. PAPS patients exhibit circulating pro-adhesive/-coagulant (TF-positive) platelets and plateletleukocyte aggregates mediated by a2GPI-D1-dependent IgG and an inflammatory trigger. While Aspirin and P2Y12 inhibitor significantly inhibited the aPL-mediated P-Selectin and TF upregulation, HCQ affected the adhesion phenotype only, and might not be adequate to prevent plateletmediated thrombosis.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"54 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547763","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":"Applying Fc-fusion proteins to tolerize perinatally and block inhibitor formation.","authors":"David W Scott","doi":"10.3324/haematol.2025.287742","DOIUrl":"https://doi.org/10.3324/haematol.2025.287742","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"185 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547736","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 retrospective study of isatuximab-pomalidomide-dexamethasone in relapsed/refractory systemic AL amyloidosis.","authors":"Sargam Rachit Vohra,Sriram Ravichandran,Darren Foard,Ana Martinez-Naharro,Lucia Venneri,Marianna Fontana,Carol J Whelan,Philip N Hawkins,Julian Gillmore,Helen J Lachmann,Shameem Mahmood,Ashutosh D Wechalekar","doi":"10.3324/haematol.2025.287664","DOIUrl":"https://doi.org/10.3324/haematol.2025.287664","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"4 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547766","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":"Hematopoietic stem cell transplantation is effective in achieving long-term survival for post-aplastic anemia myeloid neoplasms: the EBMT Severe Aplastic Anemia Report.","authors":"Pedro Henrique Prata,Dirk-Jan Eikema,Brian Piepenbroek,Austin Kulasekararaj,Beatrice Drexler,Jennifer M-L Tjon,Krista Vaht,Mahmoud Aljurf,Patrice Chevallier,Tobias Gedde-Dahl,Ain Kaare,Urpu Salmenniemi,Thomas Schroeder,Jenny Byrne,Jérôme Cornillon,Fiorenza Barraco,Johan Maertens,Eleni Tholouli,Uwe Platzbecker,Nicolaus Kröger,Didier Blaise,Simona Sica,Robert Zeiser,Antonio Maria Risitano,Régis Peffault De Latour","doi":"10.3324/haematol.2024.287205","DOIUrl":"https://doi.org/10.3324/haematol.2024.287205","url":null,"abstract":"Aplastic anemia (AA) transformation into myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) is associated with a dismal prognosis. Hematopoietic stem cell transplant offers the sole possibility of cure, but data on long-term survival are scarce. We retrospectively analyzed 270 patients transplanted for MDS, AML, or an isolated cytogenetic abnormality after a diagnosis of AA or paroxysmal nocturnal hemoglobinuria reported to the EBMT. The median age at transplantation was 39 years. The 5-year overall survival (OS) rate was 64%, unaffected by chromosome 7 abnormalities, age at transplant, sex, interval from clonal evolution to transplant, and intensity of conditioning regimen. The 5-year non-relapse mortality rates were 34% (95% CI, 25-42%) for MDS patients and 19% (95% CI, 7-31%) for AML patients and were higher following a myeloablative conditioning regimen. The five-year relapse rate was 12% (95% CI, 6-19%) for MDS and 22% (95% CI, 9-35%) for AML. Our study's survival estimates reflect a younger cohort of patients, considering the bimodal distribution of aplastic anemia. Conditioning regimen intensity did not affect relapse. For MDS patients, pretreating before transplant did not improve survival nor reduce relapse. Transplantation is feasible and effective in achieving long-term survival for transplant-eligible post-AA myeloid neoplasm patients. MDS patients may benefit from upfront RIC transplant, limiting toxicity without higher relapse. Posttransplant maintenance therapies to reduce the relapse incidence among AML patients might be warranted.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"638 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547767","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":"Ibrutinib versus acalabrutinib in fixed-duration chronic lymphocytic leukemia therapy: a comparative analysis of efficacy.","authors":"Stefano Molica,Tait D Shanafelt,Diana Giannarelli,David Allsup","doi":"10.3324/haematol.2025.288323","DOIUrl":"https://doi.org/10.3324/haematol.2025.288323","url":null,"abstract":"Not available.","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":"27 1","pages":""},"PeriodicalIF":10.1,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547772","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}