Haematologica最新文献

{"title":"Blinatumomab in induction therapy improves molecular response in untreated adults with Ph- B-cell precursor acute lymphoblastic leukemia.","authors":"Cyril Salek, Stepan Hrabovsky, Frantisek Folber, Zdenek Koristek, Jan M Horacek, Eva Fronkova, Leona Rezkova Reznickova, Pavla Pecherkova, Petr Soukup, Barbora Dluhosova, Vaclava Polivkova, Jitka Krizkova, Katerina Machova Polakova, Zuzana Vrzalova, Hana Halamova, Jan Trka, Petr Cetkovsky, Michael Doubek","doi":"10.3324/haematol.2024.287062","DOIUrl":"https://doi.org/10.3324/haematol.2024.287062","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407144","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":"Oncogenic <i>NTRK3</i> mutations exhibit differential sensitivity to tropomyosin receptor kinase inhibitors in patients with acute myeloid leukemia.","authors":"Sunil K Joshi, Ariane Huang, Janét Pittsenbarger, Ujwal Shinde, Camilo Posso, Paul D Piehowski, Sara J C Gosline, Richard D Press, Marina A Gritsenko, Chelsea Hutchinson, Karl K Weitz, Kevin Watanabe-Smith, Nicola Long, Karin D Rodland, Jeffrey W Tyner, Brian J Druker, Cristina E Tognon","doi":"10.3324/haematol.2024.285572","DOIUrl":"10.3324/haematol.2024.285572","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407147","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":"Changes in asparaginase exposure and toxicity profiles in obese pediatric acute lymphoblastic leukemia patients.","authors":"John C Panetta, Emily Ashcraft, Sima Jeha, Ching-Hon Pui, Hiroto Inaba, Seth E Karol, Cheng Cheng, Hope D Swanson","doi":"10.3324/haematol.2024.285788","DOIUrl":"https://doi.org/10.3324/haematol.2024.285788","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407145","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":"Overall cancer risk in people with deleterious germline <i>DDX41</i> variants.","authors":"Sophia C Korotev, Jason X Cheng, Yogameenakshi Haribabu, Joshua Strauss, Salina Dominguez, Ashwin Koppayi, Melody Perpich, Madeline Pies, Luke Moma, Aelin Kim, Hatice Basdag, Courtnee Rodgers, Satyajit Kosuri, Ryunosuke Saiki, Hideki Makishima, Sanjukta Tawde, Shelly Galasinski, Priscilla Kandikatla, Hari Prasanna Subramanian, Kehan Ren, Honghao Bi, Mona Mohammadhosseini, Seishi Ogawa, Peng Ji, Anupriya Agarwal, Soma Das, Lucy A Godley","doi":"10.3324/haematol.2024.286887","DOIUrl":"https://doi.org/10.3324/haematol.2024.286887","url":null,"abstract":"<p><p>Germline loss of function (LoF) DDX41 variants predispose to late-onset hematopoietic malignancies (HMs), predominantly of myeloid lineage. Among 43 families with germline DDX41 LoF variants, bone marrow (BM) biopsies in those without (n=8) or with malignancies (n=21) revealed mild dysplasia in peripheral blood (57%) and BM (88%), long before the average age of DDX41-related HM onset. Therefore, we recommend baseline bone marrow biopsies in people with germline DDX41LoF alleles to avoid over-diagnosis of myelodysplastic syndromes. A variety of solid tumors were also observed in our cohort, with 24% penetrance by age 75. Although acquired DDX41 mutations are common in HMs, we failed to identify such alleles in solid tumors arising in those with germline DDX41LoF variants (n=15), suggesting an alternative mechanism driving solid tumor development. Furthermore, 33% of pedigrees in which >15% of first-degree relatives including the proband were diagnosed with a solid tumor had second germline deleterious variants in other cancerpredisposition genes, likely serving as primary cancer drivers. Finally, both lymphoblastoid cell lines and primary peripheral blood from individuals with germline DDX41LoF variants exhibited differential levels of inflammation-associated proteins. These data provide evidence of inflammatory dysfunction mediated by germline DDX41LoF alleles that may contribute to solid tumor growth in the context of additional germline cancer-associated variants. For those with HMs and personal/family histories of solid tumors, we recommend broad germline testing. DDX41 may be an indirect modifier of solid tumor pathogenesis compared to its tumor suppressor function within hematopoietic tissues, a hypothesis that can be addressed in future work.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143407149","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":"Comprehensive characterization of platelet function in dogs with hyperadrenocorticism.","authors":"Sanggu Kim, Dohee Lee, Preeti Kumari Chaudhary, Hakhyun Kim, Byeong-Teck Kang, Soochong Kim","doi":"10.3324/haematol.2024.286496","DOIUrl":"https://doi.org/10.3324/haematol.2024.286496","url":null,"abstract":"<p><p>Hyperadrenocorticism (HAC) leads to a hypercoagulable state and contributes to the risk of thromboembolic disease. Hypercoagulation in HAC occurs in both humans and dogs. Platelets play a major role in thrombosis and hemostasis, but no study has investigated platelet function in dogs with HAC. Thus, we aimed to characterize the platelet function and its molecular mechanism in dogs with HAC by using platelets isolated from normal dogs and dogs with HAC. This prospective crosssectional study included 7 dogs with HAC and 15 normal dogs. Various platelet functional responses including platelet aggregation and dense-granule secretion were evaluated. 2-MeSADP- and low concentration of thrombin-induced platelet aggregation and secretion were significantly inhibited in dogs with HAC compared to normal dogs. Furthermore, the pre-incubation of platelets with prednisolone inhibited 2-MeSADP- and thrombin-induced platelet aggregation and secretion only in normal dog platelets, whereas no additional inhibitory effect was shown in dogs with HAC confirming a role of excessive cortisol in platelet function. In addition, 2-MeSADP- and thrombininduced platelet aggregation and post-adrenocorticotropic hormone (ACTH) cortisol levels showed a negative correlation. Moreover, 2-MeSADP- and thrombin-induced thromboxane A2 (TxA2) generation was significantly inhibited in dogs with HAC compared to normal dogs, confirming the role of cortisol in TxA2 generation. Finally, thrombin-induced ERK and AKT phosphorylation were significantly inhibited in dogs with HAC. In conclusion, excessive cortisol in dogs with HAC affects platelet function by suppressing TxA2 generation through the regulation of ERK and AKT phosphorylation.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255530","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":"Deep immunophenotypic dissection and clinical impact of T cells in the follicular lymphoma microenvironment.","authors":"Sary El Daker, David Qualls, Andriy Derkach, Samida Beqaj, Leonardo Boiocchi, Venkatraman Seshan, Jeeyeon Baik, Menglei Zhu, Gilles Salles, Ahmet Dogan, Mikhail Roshal, Pallavi Galera","doi":"10.3324/haematol.2024.286383","DOIUrl":"10.3324/haematol.2024.286383","url":null,"abstract":"<p><p>Follicular lymphoma (FL) is an indolent B cell lymphoma with a heterogenous disease course, and patients may not require immediate treatment upon diagnosis. Scrutiny of its microenvironment may provide key insights into lymphomagenesis and enhancement of therapeutic options. We analyzed the T-cell composition of a large, well-annotated follicular hyperplasia (FH; n=43) cohort utilizing standardized high dimensionality flow cytometry (>150,000 cells analyzed/sample) and a novel reproducible analytical pipeline leading to identification of even minor T-cell subsets. This baseline reference set was compared to prospectively collected FL samples (n=91) from untreated patients (FL-UT) and patients with relapsed/refractory disease (FL-RR). Compared to FH, both FL-UT and FL-RR specimens exhibited depletion of CD4+ and CD8+ naive subsets and were characterized by an immune suppressive microenvironment enriched in specific inhibitory T-cells, along with exhausted memory T-cells overexpressing varying combinations of immune checkpoint receptors. FL specimens showed enrichment of T follicular regulatory cells (TFR) and two highly suppressive regulatory T-cell (Treg) populations expressing TIGIT and CTLA4 (TC) and PD1, TIGIT, CTLA4, and TIM3 (PTCTi). FL-UT cases with either increased T-reg TC or increased T follicular helper cells (TFH) showed reduced time to first treatment (.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255615","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":"Emerging technologies of single-cell multi-omics.","authors":"Yi June Kim, Koichi Takahashi","doi":"10.3324/haematol.2022.282557","DOIUrl":"https://doi.org/10.3324/haematol.2022.282557","url":null,"abstract":"<p><p>The heterogeneity of the hematopoietic system was largely veiled by traditional bulk sequencing methods, which measure the averaged signals from mixed cellular populations. In contrast, single-cell sequencing has enabled the direct measurement of individual signals from each cell, significantly enhancing our ability to unveil such heterogeneity. Building on these advances, numerous single-cell multi-omics techniques have been developed into high-throughput, routinely accessible platforms, delineating the precise relationships among the different layers of the central dogma in molecular biology. These technologies have uncovered the intricate landscape of genetic clonality and transcriptional heterogeneity in both normal and malignant hematopoietic systems, highlighting their roles in differentiation, disease progression, and therapy resistance. This review aims to provide a brief overview of the principles of single-cell technologies, their historical development, and a subset of ever-expanding multi-omics tools, emphasizing the specific research questions that inspired their creation. Amidst the evolving landscape of single-cell multi-omics technologies, our main objective is to guide investigators in selecting the most suitable platforms for their research needs.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255617","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":"Comment on: Multimorbidity, comorbidity, frailty, and venous thromboembolism.","authors":"Maria I Zervou, George N Goulielmos","doi":"10.3324/haematol.2025.287356","DOIUrl":"https://doi.org/10.3324/haematol.2025.287356","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255525","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":"Response to Comment on: Multimorbidity, comorbidity, frailty, and venous thromboembolism.","authors":"Bengt Zöller, Jean M Connors","doi":"10.3324/haematol.2025.287469","DOIUrl":"https://doi.org/10.3324/haematol.2025.287469","url":null,"abstract":"<p><p>Not available.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255621","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":"New bispecific antibodies in diffuse large B-cell lymphoma.","authors":"Adrian G Minson, Michael J Dickinson","doi":"10.3324/haematol.2024.285343","DOIUrl":"https://doi.org/10.3324/haematol.2024.285343","url":null,"abstract":"<p><p>The CD20xCD3 T-cell-engaging bispecific antibodies are a highly active new treatment option for patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Epcoritamab and glofitamab have both been approved in over thirty countries as monotherapy for DLBCL after two prior treatment lines; odronextamab has recent European approval, and mosunetuzumab is active and is being developed as a combination partner. These agents can be safely combined with other immunotherapies and chemotherapy, and single-arm and randomised trial outcomes promise an expanding role for this class of drugs in earlier treatment lines. This review examines the clinical development of the CD20xCD3 bispecific antibodies in DLBCL, how the phase I and II trials inform their current use, and the key distinctions between the agents. We focus on the efficacy and safety of those bispecific antibodies most advanced in development. We also consider emerging understandings of resistance mechanisms. Finally, we review key ongoing trials and combinations and consider the potential future of bispecific antibodies within the sequence of available treatments for DLBCL.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":" ","pages":""},"PeriodicalIF":8.2,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255619","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}