Blood Cancer Journal最新文献

{"title":"Genotype-guided comparison of VEN/HMA versus intensive chemotherapy in newly diagnosed intermediate-risk AML: a multicenter real-world study.","authors":"Xin Chen,Yuhan Yan,Qian Cheng,Yishu Tang,Han Xiao,Ying Li,Erhua Wang,Jian Zhang,Liwen Wang,Qin Zhang,Xin Li","doi":"10.1038/s41408-025-01363-0","DOIUrl":"https://doi.org/10.1038/s41408-025-01363-0","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"30 1","pages":"153"},"PeriodicalIF":12.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235747","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":"Cytoskeletal dynamics and mitochondrial rearrangements drive cell fate upon antibody-induced complement activation in DLBCL.","authors":"Hilma J van der Horst,Tamás Csikós,Marjolein Quik,Jort J van der Schans,Klaas de Lint,Gonzalo Nuñez Moreno,Meijian Guan,Kubra Karagoz,Esther C W Breij,Kim C M Santegoets,Martine E D Chamuleau,M Guy Roukens,Marije B Overdijk,Tuna Mutis","doi":"10.1038/s41408-025-01358-x","DOIUrl":"https://doi.org/10.1038/s41408-025-01358-x","url":null,"abstract":"Complement-dependent cytotoxicity (CDC) is an important effector function of various therapeutic antibodies. Cancer resistance to CDC is primarily attributed to extracellular factors. Using diffuse large B-cell lymphoma (DLBCL) models, we elucidated intracellular evasion mechanisms. By CRISPR-Cas9 library screening, we identified mitochondrial damage and reactive oxygen species as the key intracellular drivers of CDC. CDC resistance was linked to augmented mitochondrial mass, elongated mitochondria and reduced mitophagy, and decreased expression of actin-related genes. Actin downregulation in CDC-resistant cells occurred specifically within the mitochondria, connecting mitochondrial rearrangements and cytoskeletal dynamics with resistance. Stimulating actin polymerization could partially overcome CDC resistance. Of clinical significance, we observed a positive association between the cytoskeleton and antibody responses in DLBCL patient samples. In conclusion, our study unveils novel intracellular resistance mechanisms to antibody-induced CDC, highlighting the critical roles of mitochondrial rearrangements and cytoskeletal dynamics in CDC. We propose that decreased mitochondrial actin prevents overload of the mitophagy pathway, thereby reducing CDC.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"123 1","pages":"156"},"PeriodicalIF":12.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235848","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":"Daratumumab plus lenalidomide maintenance in newly diagnosed multiple myeloma after transplant: AURIGA subgroup analyses.","authors":"Laahn Foster,Larry D Anderson,Alfred Chung,Chakra P Chaulagain,Erin Pettijohn,Andrew J Cowan,Caitlin Costello,Sarah Larson,Douglas W Sborov,Kenneth H Shain,Rebecca Silbermann,Peter Voorhees,Maria Krevvata,Huiling Pei,Sharmila Patel,Vipin Khare,Annelore Cortoos,Robin Carson,Thomas S Lin,Ashraf Badros","doi":"10.1038/s41408-025-01355-0","DOIUrl":"https://doi.org/10.1038/s41408-025-01355-0","url":null,"abstract":"In the primary analysis (32.3-month median follow-up) of the randomized, phase 3 AURIGA study (NCT03901963), daratumumab-lenalidomide (D-R) maintenance significantly improved MRD-negative conversion rates and reduced the risk of disease progression or death by 47% versus R maintenance in anti-CD38 monoclonal antibody-naïve and post-transplant MRD-positive patients with newly diagnosed MM. Here, we present a post hoc analysis across relevant subgroups, including high-risk cytogenetic abnormalities (HRCAs) per original, revised, and modified International Myeloma Society (IMS) 2024 criteria. MRD-negative (10-5) conversion rates by 12 months of maintenance were higher for D-R versus R across cytogenetically high-risk subgroups per original (31.8% vs 6.7%), revised (43.8% vs 13.3%), and modified IMS 2024 (41.2% vs 0%) criteria and cytogenetically ultra-high-risk disease (≥2 revised HRCAs; 54.5% vs 0%). Similar trends in overall MRD-negative conversion rates were observed across subgroups. D-R demonstrated a trend towards improved PFS versus R (HR [95% CI]) in cytogenetically high-risk subgroups per original (0.60 [0.21-1.70]), revised (0.53 [0.21-1.31]), and modified IMS 2024 (0.45 [0.13-1.53]) criteria and cytogenetically ultra-high-risk disease (0.61 [0.17-2.25]). Similar outcomes were observed regardless of age or race, with no additional safety concerns among older (≥65 years) or Black patients. These data support the benefit of D-R maintenance regardless of age, race, and risk status.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"24 1","pages":"154"},"PeriodicalIF":12.8,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145235749","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":"Allogeneic stem cell transplantation in chronic myelomonocytic leukemia: analysis of post-transplant survival and risk factors in 138 Mayo Clinic patients.","authors":"Ali Alsugair, Estefania Gauto Mariotti, Mohammad M Alhousani, Saubia Fathima, Muhammad Yousuf, Abiola Bolarinwa, James Foran, Abishek A Mangaonkar, Mark Litzow, Hemant Murthy, Lisa Sproat, Jeanne Palmer, Aasiya Matin, Ernesto Ayala, James Slack, Luis Porrata, Madiha Iqbal, Nandita Khera, Nathan Punwani, Saad Kenderian, Saurabh Chhabra, William J Hogan, Mithun Vinod Shah, Hassan B Alkhateeb, Naseema Gangat, Mrinal Patnaik, Ayalew Tefferi","doi":"10.1038/s41408-025-01359-w","DOIUrl":"10.1038/s41408-025-01359-w","url":null,"abstract":"<p><p>Allogeneic stem cell transplant (ASCT) remains the only curative option in chronic myelomonocytic leukemia (CMML). We retrospectively analyzed 138 CMML patients who underwent ASCT at the Mayo Clinic. Patients who transitioned to ASCT while in chronic phase (Group A) displayed superior post-transplant survival (PTS), compared to those in whom ASCT was performed after blast transformation (BT; Group B) (median 95 vs. 16 months; p = 0.01). In Group A, PTS was superior in patients with <5% bone marrow (BM) blasts at time of ASCT (median 164 vs. 13.5 months; p = 0.01). Other predictors of superior PTS included day-100 BM blast <5% or normal cytogenetics (median 164 vs. 18 months; p = 0.01) or presence of chronic graft-versus-host-disease (GVHD; median 164 vs. 26 months; p = 0.01). Pre-ASCT hypomethylating agent exposure (HR = 2.03; p = 0.03), and receiving more than one line of pre-ASCT chemotherapy (p = 0.01) predicted inferior PTS. In multivariable analysis, predictors of superior GVHD-free and relapse-free survival (GRFS) included the use of myeloablative conditioning and the absence of morphologically or cytogenetically apparent disease at day-100. The use of post-transplant cyclophosphamide (PTCy) was associated with a higher cumulative incidence of relapse (p = 0.02) and numerically inferior PTS (p = 0.1). Group B patients also appeared to benefit from achieving BM blast <5% at the time of ASCT (p = 0.4) as well as at day-100 (p = 0.01), in terms of PTS, while full chimerism and normal cytogenetics at day-100 were associated with superior GRFS. These observations support the value of ASCT in CMML, especially if performed prior to BT and in the presence of <5% BM blasts at the time of ASCT. Additionally, the observed detrimental impact of PTCy requires additional studies to confirm and investigate the underlying mechanisms.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"15 1","pages":"157"},"PeriodicalIF":11.6,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12501290/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145237776","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}

{"title":"Pediatric MDS in GATA2 deficiency, narrowing the scope.","authors":"M Tarek Elghetany","doi":"10.1038/s41408-025-01361-2","DOIUrl":"https://doi.org/10.1038/s41408-025-01361-2","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"26 1","pages":"151"},"PeriodicalIF":12.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188348","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":"Impact of residual clonal plasma cells in S-phase at the time of autologous stem cell transplantation on clinical outcomes.","authors":"Tamer Hellou,Daniel G Packard,Suheil Albert Atallah-Yunes,Ahauve M Orusa,Shinichiro Suzuki,Shaji K Kumar,Angela Dispenzieri,Saurabh Zanwar,Dragan Jevremovic,Horatiu Olteanu,Pedro Horna,Gregory Otteson,Francis K Buadi,David Dingli,Suzanne R Hayman,Prashant Kapoor,Nelson Leung,Joselle Cook,Nadine Abdallah,Moritz Binder,Eli Muchtar,Rahma Warsame,Taxiarchis V Kourelis,Ronald S Go,Yi Lin,S Vincent Rajkumar,Wilson I Gonsalves,Morie A Gertz","doi":"10.1038/s41408-025-01349-y","DOIUrl":"https://doi.org/10.1038/s41408-025-01349-y","url":null,"abstract":"Autologous stem cell transplantation (ASCT) is a key therapeutic strategy for many patients diagnosed with multiple myeloma (MM), yet early relapses post-transplant remains a major clinical challenge. The plasma cell proliferation (PCPRO) test, which quantifies the proportion of clonal plasma cells in the bone marrow in S-phase (S-phase%) offers a scalable alternative to measuring their proliferation rate compared to the older plasma cell labeling index (PCLI) assay. The impact of the S-phase% in residual clonal plasma cells at the time of ASCT is not clear. We retrospectively analyzed MM patients undergoing an ASCT within one year of diagnosis at Mayo Clinic between January 2013-August 2024. The S-phase% was determined by multiparametric flow cytometry. Patients were grouped into S-phase <2%, ≥2%, or non-assessable, reflecting low numbers of clonal plasma cells at time of ASCT. Among 1,136 patients, 372 had an S-phase <2%, 142 had an S-phase of ≥2% and 622 had non-assessable S-phase. Patients with S-phase ≥2% had higher rates of high-risk cytogenetics, ISS stage III, and elevated creatinine. Median progression-free survival (PFS) and overall survival (OS) from time of ASCT were 26 months and 57 months for patients with S-phase ≥2%, compared to 47 months and not reached for those with S-phase <2%. (P < 0.0001 for both PFS and OS). Patients with non-assessable S-phase, had the most favorable outcomes. In conclusion, our results show that S-phase% at the time of ASCT is a significant prognostic marker in MM. Notably, patients with S-phase ≥5%, and especially ≥10%, had extremely poor outcomes (median PFS of 13 and 3.5 months, respectively), identifying a functionally high-risk group that may derive little or no benefit from standard ASCT. This poor prognostic factor should lead to consideration of alternative strategies including enrollment in clinical trials evaluating novel immunotherapies such as CAR T-cells or T-cell engagers as part of first-line therapy.","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"19 1","pages":"152"},"PeriodicalIF":12.8,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188432","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":"Treatment outcomes and CNS relapse risk in patients with primary cutaneous DLBCL, leg-type in the rituximab era","authors":"Giulio Cassanello, Esther Drill, Annie Qiu, Mark D. Ewalt, Paul Hamlin, Steven M. Horwitz, Erel Joffe, Anita Kumar, Alison J. Moskowitz, Ariela Noy, Colette Owens, Maria Lia Palomba, Andrew D. Zelenetz, Ahmet Dogan, Klaus J. Busam, Joachim Yahalom, Gilles Salles, Matthew J. Matasar, Lorenzo Falchi","doi":"10.1038/s41408-025-01354-1","DOIUrl":"https://doi.org/10.1038/s41408-025-01354-1","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"52 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144919392","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":"Clustering of lymphoid neoplasms by cell of origin, somatic mutation and drug usage profiles: a multi-trait genome-wide association study","authors":"Murat Güler, Federico Canzian","doi":"10.1038/s41408-025-01351-4","DOIUrl":"https://doi.org/10.1038/s41408-025-01351-4","url":null,"abstract":"<p>Lymphoid neoplasms (LNs) are heterogeneous malignancies arising from lymphoid cells, displaying diverse clinical and molecular features. Although LNs are collectively frequent, individual subtypes are rare, posing challenges for genetic association studies. Indeed, genome-wide association studies (GWAS) explained only a fraction of the heritability. Shared genetic susceptibility and overlapping risk factors suggest a partially common etiology across subtypes. We employed a multi-trait GWAS strategy to improve discovery power by leveraging pleiotropy among LN subtypes. We defined LN phenoclusters based on cell of origin, somatic mutation profiles, and approved therapeutic agents. Using data from three large cohorts—the UK Biobank, Million Veteran Program, and FinnGen—we analyzed 31,937 LN cases and 1.2 million controls across 8 individual subtypes and 7 phenoclusters. We replicated the novel associations in two independent cohorts (All of Us and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial) with 2892 LN cases and 165,791 controls. We identified 76 genome-wide significant loci for individual subtypes or subtype clusters, including 20 novel associations. We identified the subtypes contributing to each locus, putative candidate causal variants, and genes underlying the associations, and found enrichment of specific cell types, biological processes, and drugs associated with LN risk genes. Overall, this study identified new LN genetic risk loci and candidate genes, providing insights that may inform novel therapeutic approaches.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"15 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915676","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":"Incidence and prevalence of clinically detected smoldering multiple myeloma within the general population: a retrospective observational cohort study","authors":"Adrian Wong, Victor H. Jimenez-Zepeda, Kathryn Rankin, Irwin Sandhu, Michael Chu, Aurélien Delluc, Hira Mian, Julie Stakiw, Christopher Cipkar, Arleigh McCurdy, Benjamin Patrick, Sarah Albert, Meriem Henia, Edward Koo, Hyra Sapru, Christopher McCudden, Alissa Visram","doi":"10.1038/s41408-025-01352-3","DOIUrl":"https://doi.org/10.1038/s41408-025-01352-3","url":null,"abstract":"","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"23 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915673","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":"State of the art biology, progression, and clinical management of monoclonal B-cell lymphocytosis (MBL): consensus report from the Intercepting Blood Cancers Workshop Committee","authors":"Christine E. Ryan, Inhye E. Ahn, Aswin Sekar, Andrew Rawstron, Julia Almeida, Iñaki Martin-Subero, Erin M. Parry, Miguel Alcoceba, Dinis P. Calado, Alberto Orfao, Anton W. Langerak, Hendrik Veelken, Petra Langerbeins, Deborah M. Stephens, Sameer A. Parikh, Carsten U. Niemann, Sandrine Roulland, Kostas Stamatopoulos, Susan L. Slager, Tait Shanafelt, Paolo Ghia, Jessica Okosun, Matthew S. Davids","doi":"10.1038/s41408-025-01341-6","DOIUrl":"https://doi.org/10.1038/s41408-025-01341-6","url":null,"abstract":"<p>In March 2023 and 2024, a panel of international experts convened at the first and second Intercepting Blood Cancers (IBC) Workshops, with the aim of better appreciating the diagnostic challenges, pathophysiology, and potential therapeutic interventions for precursor malignant hematology conditions. Here, we report a summary of the proceedings from the sessions focused on monoclonal B-cell lymphocytosis (MBL)/chronic lymphocytic leukemia (CLL). We highlight four main content areas: biology of MBL, clinical implications of MBL, progression of MBL and transformation from indolent CLL to aggressive disease, and opportunities for therapeutic intervention in early CLL. We additionally outline key consensus management recommendations and research goals.</p>","PeriodicalId":8989,"journal":{"name":"Blood Cancer Journal","volume":"35 1","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915674","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}