Seminars in hematology最新文献_第2页

Closing the disease modification gap: Emerging therapies in myelofibrosis beyond JAK inhibition 缩小疾病修饰差距：超越JAK抑制的骨髓纤维化新疗法

IF 4.3 3区医学

Seminars in hematology Pub Date : 2026-04-01 Epub Date: 2026-07-30 DOI: 10.1053/j.seminhematol.2026.07.002

Akshay Aluri, Ashwin Kishtagari

{"title":"Closing the disease modification gap: Emerging therapies in myelofibrosis beyond JAK inhibition","authors":"Akshay Aluri, Ashwin Kishtagari","doi":"10.1053/j.seminhematol.2026.07.002","DOIUrl":"10.1053/j.seminhematol.2026.07.002","url":null,"abstract":"<div><div>Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by dysregulated myeloid proliferation and hyperactive JAK-STAT signaling pathway. While JAK inhibitors have become standard therapies for the management of these conditions, significant challenges remain due to resistance to these medications and adverse effects such as cytopenias and infectious complications. This review explores novel therapeutic strategies that target pathways beyond JAK-STAT signaling. We discuss BET inhibitors (pelabresib), PIM kinase inhibitors (TP-3654), telomerase inhibition (imetelstat), nuclear export inhibition (selinexor), LSD1 inhibition (bomedemstat), MDM2 antagonism (navtemadlin), mutant CALR-directed immunotherapies, and activin receptor ligand traps (elritercept). Emerging data suggest that pairing JAK inhibitors with agents that target transcriptional regulation, clonal persistence, anemia, or fibrosis can demonstrate improved responses and enhance safety profiles. Strategies such as high-molecular-risk mutation profiling and variant allele frequency monitoring to assess disease progression and clonal burden will also be discussed. As the focus of MPN management shifts towards curative nontransplant options, a combination of improved access to clinical trials and accounting for patient-reported outcomes will be vital if we are to realize the promise of these next-generation therapies.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"63 2","pages":"Pages 118-125"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888573","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Myeloproliferative Neoplasms: Finding Our Footing in a Shifting Landscape 骨髓增生性肿瘤：在不断变化的环境中寻找我们的立足点

IF 4.3 3区医学

Seminars in hematology Pub Date : 2026-04-01 Epub Date: 2026-10-16 DOI: 10.1053/j.seminhematol.2026.10.001

Anand A. Patel

引用次数: 0

Cardiovascular complications in patients with myeloproliferative neoplasms: What hematologists need to know 骨髓增殖性肿瘤患者的心血管并发症：血液学家需要知道的。

IF 4.3 3区医学

Seminars in hematology Pub Date : 2026-04-01 Epub Date: 2026-05-14 DOI: 10.1053/j.seminhematol.2026.05.005

Orly Leiva, Olivia C. Liu, Monica Ferrante, Vasilios P. Katsadouros, Gabriela Hobbs

引用次数: 0

outside front cover, PMS 8883 metallic AND 4/C 外部前盖，PMS 8883金属和4/C

IF 4.3 3区医学

Seminars in hematology Pub Date : 2026-04-01 Epub Date: 2026-10-16 DOI: 10.1053/S0037-1963(26)00102-2

引用次数: 0

Treatment of myeloproliferative neoplasms: Exploring new horizons of who and when to cytoreduce in patients with polycythemia vera and essential thrombocytosis 骨髓增殖性肿瘤的治疗：真性红细胞增多症和原发性血小板增多症患者谁和何时进行细胞减少的新视野。

IF 4.3 3区医学

Seminars in hematology Pub Date : 2026-04-01 Epub Date: 2026-06-03 DOI: 10.1053/j.seminhematol.2026.06.003

Katherine J. Feder, Gabriela S. Hobbs

{"title":"Treatment of myeloproliferative neoplasms: Exploring new horizons of who and when to cytoreduce in patients with polycythemia vera and essential thrombocytosis","authors":"Katherine J. Feder, Gabriela S. Hobbs","doi":"10.1053/j.seminhematol.2026.06.003","DOIUrl":"10.1053/j.seminhematol.2026.06.003","url":null,"abstract":"<div><div>Treatment for the classical Philadelphia-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV) and essential thrombocythemia (ET), has long relied on reducing thrombotic risk without a focus on underlying disease modification. The simplified framework of age and thrombosis history inadequately captures the biological complexity of these diseases with emerging data identifying leukocytosis, elevated neutrophil-to-lymphocyte ratio, and high <em>JAK2</em> V617F variant allele frequency as independent predictors of thrombotic risk. Furthermore, prognostic models such as MIPSS-PV and MIPSS-ET incorporate somatic mutations to better predict survival. Despite these advances, real-world practice remains anchored to traditional risk categories, with over 30% of high-risk patients receiving no cytoreductive therapy. In this evidence-based review, we trace the evolution of risk stratification in PV and ET and examine the clinical evidence supporting current cytoreductive options, specifically hydroxyurea, interferons, ruxolitinib, and anagrelide. We argue for a paradigm shift away from binarily driven thrombosis-centric risk stratification toward a personalized, proactive approach that integrates molecular and inflammatory biomarkers, expands the population offered cytoreduction, and prioritizes disease-modifying therapies. Prospective studies are needed to validate the incorporation of these markers into risk-adapted algorithms and to define the long-term impact of early disease modification on transformation, survival, and quality of life.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"63 2","pages":"Pages 91-102"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148353399","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}

引用次数: 0

Management of myeloproliferative neoplasms in pregnancy: Essential thrombocythemia, polycythemia vera, and primary myelofibrosis 妊娠期骨髓增生性肿瘤的治疗：原发性血小板增多症、真性红细胞增多症和原发性骨髓纤维化。

IF 4.3 3区医学

Seminars in hematology Pub Date : 2026-04-01 Epub Date: 2026-07-01 DOI: 10.1053/j.seminhematol.2026.06.005

Kristen Corrao

{"title":"Management of myeloproliferative neoplasms in pregnancy: Essential thrombocythemia, polycythemia vera, and primary myelofibrosis","authors":"Kristen Corrao","doi":"10.1053/j.seminhematol.2026.06.005","DOIUrl":"10.1053/j.seminhematol.2026.06.005","url":null,"abstract":"<div><div>Pregnancy in patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) is uncommon but clinically challenging. Essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF) are clonal hematopoietic stem cell disorders characterized by myeloid proliferation, JAK-STAT pathway activation, and an increased risk of thrombotic and hemorrhagic complications. Pregnancy itself is a hypercoagulable state, and when it occurs in patients with MPNs, maternal and fetal complications are more frequent than in the general population. The most common fetal complications are first trimester pregnancy loss, placental insufficiency, fetal growth restriction, preeclampsia, preterm delivery, and stillbirth. Maternal complications include venous and arterial thrombosis, bleeding, acquired von Willebrand syndrome, and postpartum thromboembolism. ET is the most frequently encountered MPN in pregnancy and generally carries the most favorable prognosis. PV is associated with higher thrombotic and placental risk, largely related to erythrocytosis and hyperviscosity. Pregnancy in PMF is rare, and available data are limited to small series and case reports, making management particularly dependent on expert opinion. The mainstay of treatment is risk-adapted therapy with low-dose aspirin, low-molecular-weight heparin, phlebotomy for PV, and interferon-based cytoreduction when needed. Hydroxyurea, anagrelide, and JAK inhibitors are generally avoided due to limited fetal safety data. Given the paucity of prospective evidence, management should be individualized and coordinated by hematology and maternal-fetal medicine specialists. This review summarizes current data on MPN pregnancy outcomes and provides a practical approach to preconception counseling, antepartum management, delivery planning, postpartum care, and future research priorities.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"63 2","pages":"Pages 103-109"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148697845","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}

引用次数: 0

Current landscape and future directions for treatment of accelerated-phase and blast-phase myeloproliferative neoplasms 加速期和母细胞期骨髓增生性肿瘤治疗的现状和未来方向。

IF 4.3 3区医学

Seminars in hematology Pub Date : 2026-04-01 Epub Date: 2026-04-19 DOI: 10.1053/j.seminhematol.2026.04.003

Rohan K. Achar, Jan Philipp Bewersdorf

{"title":"Current landscape and future directions for treatment of accelerated-phase and blast-phase myeloproliferative neoplasms","authors":"Rohan K. Achar, Jan Philipp Bewersdorf","doi":"10.1053/j.seminhematol.2026.04.003","DOIUrl":"10.1053/j.seminhematol.2026.04.003","url":null,"abstract":"<div><div>Philadelphia chromosome-negative myeloproliferative neoplasms (MPN) are clonal hematopoietic stem cell disorders that carry the risk of transformation to accelerated-phase MPN (MPN-AP) and blast-phase MPN (MPN-BP) characterized by 10% to 19% and ≥20% peripheral or circulating blasts, respectively. This leukemic transformation is associated with less than 6 to 9 months of median overall survival and remains a major clinical challenge with limited effective treatment options. The biology of MPN-AP/BP is distinct from the pathophysiology of <em>de novo</em> acute myeloid leukemia (AML) and is characterized by complex clonal evolution with acquired somatic mutations in epigenetic regulators, RNA splicing factors, and <em>TP53</em>. Standardized risk stratification and treatment response frameworks built specifically for this disease group are not yet widely used. This limits optimal clinical trial design and meaningful cross-study comparison. The only curative treatment for MPN-AP/BP remains allogeneic hematopoietic stem cell transplant, but there is no standard of care for transplant-ineligible patients or for bridging therapy prior to transplant. Based on non-randomized trials and retrospective cohorts, less-intensive treatment regimens are often preferred except for fit patients with <em>TP53</em> wild-type disease who may derive benefit from standard induction chemotherapy. Less-intensive strategies generally combine hypomethylating agents with anti-apoptotic or targeted agents. Given the role of <em>IDH1</em> and <em>IDH2</em> mutations in leukemic transformation, targeted therapies with IDH1 or IDH2 inhibitors are another option for selected patients. Current studies are investigating the role of next-generation Janus Kinase (JAK) inhibition, inhibition of epigenetic modulators, and blockade of anti-apoptotic pathways as paradigm shifts to make MPN-AP/BP a more manageable disease.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"63 2","pages":"Pages 126-135"},"PeriodicalIF":4.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147975136","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}

引用次数: 0

Evolving insights into mitochondrial presence in RBC in sickle cell disease: Red blood cell and reticulocyte pathophysiology, therapeutic strategies, and future directions 镰状细胞病中红细胞线粒体存在的进化见解：红细胞和网织红细胞病理生理、治疗策略和未来方向

IF 4.3 3区医学

Seminars in hematology Pub Date : 2026-02-01 Epub Date: 2026-05-09 DOI: 10.1053/j.seminhematol.2026.05.003

Yaw Ansong-Ansongton, Daisy Zapet Bamac, Angela Rivers

{"title":"Evolving insights into mitochondrial presence in RBC in sickle cell disease: Red blood cell and reticulocyte pathophysiology, therapeutic strategies, and future directions","authors":"Yaw Ansong-Ansongton, Daisy Zapet Bamac, Angela Rivers","doi":"10.1053/j.seminhematol.2026.05.003","DOIUrl":"10.1053/j.seminhematol.2026.05.003","url":null,"abstract":"<div><div>Recent advances in understanding sickle cell disease (SCD) pathophysiology have revealed the critical role of abnormal mitochondrial retention in mature erythrocytes. This comprehensive review examines how disrupted mitochondrial clearance contributes to disease progression through multiple mechanisms, including oxidative stress, metabolic dysfunction, and immune activation. We will review evidence from both human studies and animal models demonstrating that retained mitochondria remain functionally active and contribute to cellular damage. Furthermore, we will highlight emerging findings that active mitochondria in reticulocytes are also detrimental in SCD, exacerbating oxidative stress, and promoting premature cellular damage. This review examines therapeutic approaches targeting mitochondrial dysfunction, including pyruvate kinase activation and mitophagy enhancement strategies. Understanding these mechanisms provides new opportunities for therapeutic intervention in SCD and related disorders.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"63 1","pages":"Pages 37-50"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148158065","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}

引用次数: 0

The paradox of HbSC disease—Not so benign after all HbSC疾病的悖论——毕竟不是那么良性。

IF 4.3 3区医学

Seminars in hematology Pub Date : 2026-02-01 Epub Date: 2026-05-10 DOI: 10.1053/j.seminhematol.2026.05.001

Randolph B. Lyde, Enrico M. Novelli

引用次数: 0

The many facets of cardiopulmonary complications in sickle cell disease 镰状细胞病心肺并发症的许多方面。

IF 4.3 3区医学

Seminars in hematology Pub Date : 2026-02-01 Epub Date: 2026-06-06 DOI: 10.1053/j.seminhematol.2026.05.007

Thomas d’Humières, Sylvain Le Jeune, Gonzalo de Luna, Thibaut Moulin, Laurent Boyer, Haytham Derbel, Sihem Iles, Nicolas Lellouche, Antonio Fiore, Geneviève Derumeaux, Pablo Bartolucci, Armand Mekontso Dessap, Laurent Savale

{"title":"The many facets of cardiopulmonary complications in sickle cell disease","authors":"Thomas d’Humières, Sylvain Le Jeune, Gonzalo de Luna, Thibaut Moulin, Laurent Boyer, Haytham Derbel, Sihem Iles, Nicolas Lellouche, Antonio Fiore, Geneviève Derumeaux, Pablo Bartolucci, Armand Mekontso Dessap, Laurent Savale","doi":"10.1053/j.seminhematol.2026.05.007","DOIUrl":"10.1053/j.seminhematol.2026.05.007","url":null,"abstract":"<div><div>Sickle cell disease (SCD) is a systemic vasculopathy, which progressively remodels the heart and pulmonary circulation through chronic anemia, hemolysis, and endothelial dysfunction. This review integrates current evidence on the mechanisms, clinical spectrum, and management of SCD-related cardiopulmonary complications. Chronic anemia drives a high-output state characterized by cardiac chamber dilation leading to eccentric remodeling that, over time, may evolve toward diastolic dysfunction, heart failure with preserved ejection fraction (HFpEF), and postcapillary pulmonary hypertension (PH). Concomitant hemolysis, oxidative stress, and microvascular injury promote diffuse myocardial fibrosis that acts as an arrhythmogenic substrate underlying both atrial and ventricular arrhythmias (VAs). Beyond left-sided cardiac disease, SCD also contributes to pulmonary vascular injury and “relative systemic hypertension”, both reflecting a vasculopathy process that amplifies target organs damage. Transthoracic echocardiography (TTE) remains the cornerstone of diagnosis and prognosis of SCD-related cardiomyopathy, enabling longitudinal assessment of ventricular performance, chamber remodeling and hemodynamics including pulmonary pressures, while cardiac magnetic resonance (CMR) adds information on tissue characterization and quantification of diffuse fibrosis. Emerging data suggests that curative therapies. Such as hematopoietic stem cell transplantation and gene therapy can reverse cardiac remodeling and fibrosis yet necessitate structured long-term follow-up. Recognizing SCD-related cardiomyopathy as a dynamic and potentially reversible cardiopulmonary continuum is essential for establishing disease-specific diagnostic criteria and guiding physiological grounded therapeutic strategies.</div></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"63 1","pages":"Pages 16-27"},"PeriodicalIF":4.3,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148353471","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}

引用次数: 0