Seminars in hematology最新文献

{"title":"Secondary and therapy-related acute myeloid leukemias: Overlapping features, distinct trajectories.","authors":"Luca Guarnera, Emiliano Fabiani, Giorgia Silvestrini, Enrico Attardi, Maria Teresa Voso","doi":"10.1053/j.seminhematol.2025.06.005","DOIUrl":"https://doi.org/10.1053/j.seminhematol.2025.06.005","url":null,"abstract":"<p><p>Therapy-related acute myeloid leukemia (tAML) and AML arising from previous hematologic disorders (secondary AML, sAML) share similar biological features, including karyotype abnormalities and gene specific mutations, patient-related risk factors. Older age and lower performance status also contribute to dimal prognosis, and dismal prognosis, both in terms of response rate and overall survival. However, these 2 entities significantly differ in leukemogenic trajectories. In this line, recent advances allowed for a better understanding of differential clonal progression processes in the broad landscape of sAMLs. Thus, in this manuscript, we reviewed clinical and biological characteristics of tAML and sAML, highlighting commonalities and divergent features and discussed classification aspects. We also gathered the newest evidence of leukemogenic trajectories leading from bone marrow failure syndromes, myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN) and MDS/MPN overlap syndromes to sAML, as well as leukemias arising from donors' cells in the setting of allogenic transplantation. Furthermore, we reviewed germline and acquired predisposition to leukemias and discussed the therapeutic landscape and future directions.</p>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718388","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic dysregulation in acute myeloid leukemia.","authors":"Jens Schrezenmeier, B J P Huntly","doi":"10.1053/j.seminhematol.2025.06.003","DOIUrl":"https://doi.org/10.1053/j.seminhematol.2025.06.003","url":null,"abstract":"<p><p>Acute myeloid leukemia (AML) is an aggressive hematologic malignancy defined by the clonal expansion of undifferentiated myeloid blasts with a block in differentiation and aberrant self-renewal. While recurrent genomic mutations are well-documented in AML, epigenetic dysregulation has emerged as an equally pivotal driver of leukemogenesis, a notion corroborated by the frequent recurrence of mutations in epigenetic regulators. Leukemic cells exhibit pervasive epigenetic alterations-including abnormal DNA methylation patterns, dysregulated histone modification, disrupted chromatin architecture and RNA-based regulatory mechanisms -which collectively rewire gene expression programs. These changes silence key differentiation genes and sustain self-renewal pathways, enforcing the developmental arrest and hyper-proliferation that are the hallmarks of AML. Importantly, epigenetic aberrations in AML are not merely downstream consequences of genetic lesions but actively contribute to the malignant phenotype. Somatic mutations frequently target epigenetic regulators (for example, DNA methyltransferases or histone modifiers), and these lesions cooperate with other genetic alterations to initiate and maintain the leukemic clone. Together, these insights highlight epigenetic dysregulation as a central mechanism in AML pathogenesis.</p>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144619987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AML diagnostics in the 21st century: Use of AI.","authors":"Torsten Haferlach, Jan-Niklas Eckardt, Wencke Walter, Sven Maschek, Jakob Nikolas Kather, Christian Pohlkamp, Jan Moritz Middeke","doi":"10.1053/j.seminhematol.2025.06.002","DOIUrl":"https://doi.org/10.1053/j.seminhematol.2025.06.002","url":null,"abstract":"<p><p>The landscape of acute myeloid leukemia (AML) diagnostics is undergoing a pivotal shift towards a transformative era, driven by the integration of artificial intelligence (AI). This review delves into the pivotal role of AI in reshaping AML diagnostics in the 21st century, highlighting advancements, challenges, and future prospects. AML, marked by the immediate need for accurate diagnosis and treatment, requires precise analysis against the complexity of various diagnostic methods such as cytomorphology, immunophenotyping, cytogenetics, and molecular testing. The introduction of AI in this field promises to address the critical need for rapid and standardized diagnostics, thereby enhancing patient care. AI technologies, including deep learning (DL) and machine learning (ML), are revolutionizing the interpretation of complex diagnostic data. With the use of AI-based models such as deep learning (DL) classifiers or automated karyotyping, promising tools do already exist. When it comes to reporting and reasoning, large language models (LLM) show their potential in efficient data processing and better clinical decision-making. This includes the use of large language models (LLMs) for generating comprehensive diagnostic reports that integrate multi-layered diagnostic information. However, there is a critical need for transparency and interpretability in AI-driven diagnostics. Explainable AI (XAI) models address this need building trust among clinicians and patients. Moreover, this review addresses the growing field of synthetic data that are becoming increasingly accessible due to advances in AI and computational technology. While synthetic data present a promising avenue for augmenting clinical research and potentially optimizing clinical trials in fields such as AML, their application requires careful ethical, regulatory, and methodological considerations. There are several limitations and challenges to consider regarding not only synthetic data but also AI models in general. This includes regulatory hurdles due to the dynamic nature of AI, as well as data privacy concerns and interoperability between different systems. In conclusion, AI has the potential to completely change how we diagnose and treat AML by offering faster, more accurate, and more comprehensive diagnostic insights. This potential is especially crucial for preserving knowledge in times of shortages of human experts. However, realizing this potential will require overcoming significant challenges and fostering collaboration between technologists and clinicians. As we move forward, the synergy between AI and human expertise will undoubtedly redefine the landscape of AML diagnostics, leading in a new era of precision medicine in hematology.</p>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measurable residual disease monitoring in acute myeloid leukaemia: Techniques, timing and therapeutic implications.","authors":"Kasper J Croese, Jacqueline Cloos, Jesse M Tettero","doi":"10.1053/j.seminhematol.2025.06.004","DOIUrl":"https://doi.org/10.1053/j.seminhematol.2025.06.004","url":null,"abstract":"<p><p>The detection of measurable residual disease (MRD) in acute myeloid leukaemia (AML) has emerged as one of the strongest prognostic indications of adverse outcomes across different treatment settings and disease stages, independent of baseline genetic risk classification. Multiple techniques for MRD-assessment have been developed and clinically validated, including multiparameter flow cytometry (MFC) and molecular assays such as quantitative PCR (qPCR) and next-generation sequencing (NGS). These approaches have been incorporated into routine clinical practice to evaluate treatment efficacy and refine disease risk stratification. Beyond the prognostic significance, MRD monitoring offers a powerful tool for monitoring subclinical disease, enabling early relapse detection and influencing therapeutic decisions, including consolidation strategies, transplant conditioning, and pre-emptive interventions. In non-intensive treatment settings, MRD may help tailor treatment duration and identify patients eligible for therapy cessation. As the therapeutic landscape of AML continues to evolve with novel agents and strategies, the role and clinical applications of MRD are becoming increasingly relevant. This review summarizes current MRD assessment techniques, optimal measurement timepoints, and clinical applications across different therapeutic settings. We also highlight ongoing innovations and future directions that aim to fully integrate MRD into precision management of patients with AML.</p>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The genomic landscape of acute myeloid leukemia: Redefining classifications, ontogeny, and therapeutic strategies.","authors":"Nicolas Duployez, Claude Preudhomme","doi":"10.1053/j.seminhematol.2025.06.001","DOIUrl":"https://doi.org/10.1053/j.seminhematol.2025.06.001","url":null,"abstract":"<p><p>Over the past decades, the progressive identification of chromosomal abnormalities and gene mutations has transformed acute myeloid leukemia (AML) from a morphologically defined disease into a genetically stratified malignancy. The coexistence and competition of multiple mutations within leukemic clones underscore the complexity of AML and the need for therapeutic strategies that address clonal interference and mutational synergy. Molecular profiling now offers a more accurate definition of AML ontogeny, surpassing clinical history and revealing biologically and prognostically distinct subtypes. At the same time, new classifications focusing on genetic characteristics have enabled a more coherent and clinically meaningful categorization of the disease. These advances have contributed directly to risk stratification and treatment selection, and thus to more appropriate management.</p>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":" ","pages":""},"PeriodicalIF":5.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"outside front cover, PMS 8883 metallic AND 4/C","authors":"","doi":"10.1053/S0037-1963(25)00019-8","DOIUrl":"10.1053/S0037-1963(25)00019-8","url":null,"abstract":"","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"62 2","pages":"Page CO1"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Report of Consensus Panel 5 from the 12th International Workshop on Waldenstrom's Macroglobulinemia on the management of patients with intolerance or resistance to covalent BTK inhibitors","authors":"Jorge J. Castillo ,&nbsp;Francesco Autore ,&nbsp;Neil L. Berinstein ,&nbsp;Andrew R. Branagan ,&nbsp;Meletios A. Dimopoulos ,&nbsp;Carlos Fernandez de Larrea ,&nbsp;Simone Ferrero ,&nbsp;Prashant Kapoor ,&nbsp;Efstathios Kastritis ,&nbsp;Jahanzaib Khwaja ,&nbsp;Monique C. Minnema ,&nbsp;Lugui Qiu ,&nbsp;John F. Seymour ,&nbsp;Josephine M.I. Vos ,&nbsp;Christopher J. Patterson ,&nbsp;Christian Buske ,&nbsp;Jeffrey V. Matous ,&nbsp;Steven P. Treon ,&nbsp;M. Lia Palomba","doi":"10.1053/j.seminhematol.2025.04.004","DOIUrl":"10.1053/j.seminhematol.2025.04.004","url":null,"abstract":"<div><div>Over the last decade, covalent Bruton tyrosine kinase (BTK) inhibitors have become a standard option for treating patients with symptomatic Waldenström Macroglobulinemia (WM) in the frontline or relapsed settings. However, the definition of intolerance and resistance to covalent BTK inhibitors has not been established. Understanding the best approaches to managing such patients is crucial to avoiding premature abandonment of effective therapy or pursuing futile therapies unlikely to be effective in controlling symptomatic disease progression. With the advent of noncovalent BTK inhibitors and BCL2 antagonists, in addition to clinical trials evaluating phospholipid-drug conjugates, antibody-drug conjugates, and bispecific antibodies, the present Consensus Panel 5 aims to establish working definitions for intolerance and resistance to covalent BTK inhibitors, as well as provide strategies to identify and manage these issues not infrequently encountered in clinical practice.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"62 2","pages":"Pages 113-119"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Report of Consensus Panel 4 from the 12th International Workshop on Waldenstrom's Macroglobulinemia on the management of patients with non-IgM lymphoplasmacytic lymphoma","authors":"Alessandra Tedeschi ,&nbsp;Rebecca Auer ,&nbsp;Francesco Autore ,&nbsp;Jorge J. Castillo ,&nbsp;Moshe E. Gatt ,&nbsp;Eva Kimby ,&nbsp;David F. Moreno ,&nbsp;Roger G. Owen ,&nbsp;Lugui Qiu ,&nbsp;Aldo M. Roccaro ,&nbsp;Shayna Sarosiek ,&nbsp;Naohiro Sekiguchi ,&nbsp;John F. Seymour ,&nbsp;Marzia Varettoni ,&nbsp;Christopher J. Patterson ,&nbsp;Jeffrey V. Matous ,&nbsp;Christian Buske ,&nbsp;Steven P. Treon ,&nbsp;Ramon Garcia Sanz","doi":"10.1053/j.seminhematol.2025.04.002","DOIUrl":"10.1053/j.seminhematol.2025.04.002","url":null,"abstract":"<div><div>Approximately 95% of lymphoplasmacytic lymphomas (LPL) are IgM secreting and are characterized as Waldenstrom Macroglobulinemia (WM). Conversely, non-IgM secreting LPL are rare. As part of the 12th International Workshop on WM (IWWM-12), a consensus panel of experts was tasked to develop recommendations for the management and response assessment of non-IgM LPL. The panel considered that in view of available molecular, pathological and clinical data, non-IgM LPL should be considered as a separate sub-entity of LPL. The panel further recommended that the IWWM-2 consensus criteria used for IgM LPL (WM) treatment initiation, should also be used for non-IgM LPL and be independent of IgG or IgA paraprotein level unless symptomatic hyperviscosity is present. The panel agreed that based on current evidence, there is insufficient data to support a different clinical management for non-IgM vs IgM (WM) LPL. Moreover, the panel advised that patients with non-IgM LPL should be treated in a similar manner to patients with IgM LPL independent of MYD88 mutation status until more is known about its impact on treatment outcomes for non-IgM LPL patients. The panel therefore recommends the use of the IWWM-11 IgM LPL (WM) response criteria for cases of non-IgM LPL with a monoclonal IgA or IgG paraprotein component, but creating a specific panel to develop formal response criteria for this LPL subset was also recommended.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"62 2","pages":"Pages 106-112"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Report of Consensus Panel 3 from the 12th International Workshop on Waldenstrom's Macroglobulinemia on the management of patients with high-risk disease","authors":"Prashant Kapoor ,&nbsp;Meletios A. Dimopoulos ,&nbsp;Stephen M. Ansell ,&nbsp;Efstathios Kastritis ,&nbsp;Ranjana Advani ,&nbsp;Eric Durot ,&nbsp;Pierre Morel ,&nbsp;Charalampia Kyriakou ,&nbsp;Roman Hajek ,&nbsp;Daniela Drandi ,&nbsp;Jithma P. Abeykoon ,&nbsp;Signy Chow ,&nbsp;Xinxin Cao ,&nbsp;Christopher J. Patterson ,&nbsp;Jeffrey V. Matous ,&nbsp;Christian Buske ,&nbsp;Steven P. Treon ,&nbsp;Marie J. Kersten","doi":"10.1053/j.seminhematol.2025.04.001","DOIUrl":"10.1053/j.seminhematol.2025.04.001","url":null,"abstract":"<div><div>The Consensus Panel 3 (CP3) of the 12th International Workshop on Waldenström macroglobulinemia (IWWM-12) has reviewed and incorporated current data to make recommendations for the management of patients with high-risk WM (HR-WM). Recognizing the considerable heterogeneity in survival outcomes and identifying a subgroup of patients with a very poor prognosis, the key recommendations from CP3 include: (1) Risk stratifying patients with smoldering WM (SWM) and active (symptomatic) WM at diagnosis (2) Using the degree of i) bone marrow lymphoplasmacytosis, ii) serum beta-2 microglobulin (β2M) elevation, iii) IgM increase, iv) serum albumin decrease and the presence of wild-type <em>MYD88</em> status markers that adversely dictate the time-to-progression from smoldering to active WM to the define HR-SWM. (3) Among patients with active WM, the presenting parameters: advanced chronological age, low serum albumin, elevated serum lactate dehydrogenase, elevated β2M and the presence of <em>TP53</em> alterations <em>(TP53</em> mutation or deletion 17p) unfavorably impact the prognosis and should be utilized to risk-stratify patients into the HR category. (4) The panel encourages screening for genetic alterations at diagnosis, prior to initiating therapy and also with rapidly advancing disease or refractoriness to ongoing therapy, which might result from clonal evolution. Although limited data directing the selection and sequencing of therapies exist, a risk-adapted approach and clinical trial participation for patients with HR-WM are highly encouraged.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"62 2","pages":"Pages 90-105"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Report of Consensus Panel 1 from the 12th International Workshop on the management of patients with IgM and Waldenstrom's Macroglobulinemia related neuropathy","authors":"Shirley D'Sa ,&nbsp;Jahanzaib Khwaja ,&nbsp;Signy Chow ,&nbsp;Meletios A. Dimopoulos ,&nbsp;Irene Dogliotti ,&nbsp;Moshe E. Gatt ,&nbsp;Roman Hajek ,&nbsp;Jindriska Lindsay ,&nbsp;Giampaolo Merlini ,&nbsp;Pierre Morel ,&nbsp;Alessandra Tedeschi ,&nbsp;Claudio Cerchione ,&nbsp;Merav Leiba ,&nbsp;Christopher J. Patterson ,&nbsp;Steven P. Treon ,&nbsp;Christian Buske ,&nbsp;Jeffrey V. Matous ,&nbsp;Marzia Varettoni ,&nbsp;Josephine M.I. Vos ,&nbsp;Filip Eftimov ,&nbsp;Efstathios Kastritis","doi":"10.1053/j.seminhematol.2025.04.006","DOIUrl":"10.1053/j.seminhematol.2025.04.006","url":null,"abstract":"<div><div>The IgM-related peripheral neuropathies (IgM-PN) are a group of chronic disorders characterized by the presence of monoclonal IgM that may be associated with one of several diseases affecting the peripheral nerves. In many cases, there is a monoclonal IgM associated with activity against neural targets, leading to progressive peripheral nerve demyelination. Neurological symptoms in this setting can also result from direct invasion of the peripheral or central nervous system by lymphoplasmacytic cells (neurolymphomatosis and Bing-Neel syndrome respectively) or via other mechanisms (for example AL amyloid deposition or cryoglobulinemic vasculitis). There is an expanding array of treatment options, but high-quality data are sparse. Diagnostic accuracy is important and needs collaboration between hematologists and neuromuscular specialists to determine the sequence and intensity of investigations. Appropriate causal attribution to the IgM disorder is essential to enable the correct therapeutic intervention. The aims of treatment intervention should be clear and realistic. Consistent and clinically meaningful measures are needed to capture treatment success. Despite therapeutic advances, many patients experience persistent disability, highlighting the need for further research.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"62 2","pages":"Pages 76-84"},"PeriodicalIF":5.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144128580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}