Seminars in hematology最新文献

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Report of Consensus Panel 2 from the 12th International Workshop on the management of Bing-Neel syndrome in patients with Waldenstrom’s Macroglobulinemia 第12届Waldenstrom巨球蛋白血症患者Bing-Neel综合征管理国际研讨会共识小组2报告。

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2025-04-01 DOI: 10.1053/j.seminhematol.2025.04.005

Shayna Sarosiek , Anne-Marie L. Becking , Andrew Branagan , Simone Ferrero , Jahanzaib Khwaja , Eva Kimby , Damien Roos-Weil , Naohiro Sekiguchi , Marek Trneny , Shuhua Yi , Christopher J. Patterson , Christian Buske , Jeffrey V. Matous , Steven P. Treon , Monique C. Minnema

Consensus panel 2 from the 12th International Workshop on Waldenstrom Macroglobulinemia was tasked with updating the guidelines on the diagnosis and management of patients with Bing-Neel syndrome (BNS). In this panel we have summarized the clinical symptoms that may be present with BNS, discussed the criteria required for diagnosis of BNS, made recommendations for follow-up imaging, and proposed revised guidelines for response assessment in BNS. The key recommendations from the 12th International Workshop on WM (IWWM-12) Consensus panel 2 include: (1) the establishment of zanubrutinib as a standard therapy for treatment of BNS; (2) recommendations on imaging and CSF evaluation during treatment and follow-up of BNS; and (3) revised response criteria in view of new data showing that malignant cells can persist in the CSF of many patients treated with BTK-inhibitors. New categorical response categories proposed include that for a Clinical Complete Response and Progressive Disease.

来自第12届华登斯特罗姆巨球蛋白血症国际研讨会的共识小组2的任务是更新Bing-Neel综合征（BNS）患者的诊断和管理指南。在这个小组中，我们总结了BNS可能出现的临床症状，讨论了BNS诊断所需的标准，提出了随访影像学的建议，并提出了BNS反应评估的修订指南。来自第12届WM国际研讨会（iwm -12）共识小组2的主要建议包括：(1)建立zanubrutinib作为治疗BNS的标准疗法；(2) BNS治疗及随访时影像学及脑脊液评价建议；(3)鉴于新的数据显示，在许多接受btk抑制剂治疗的患者脑脊液中，恶性细胞可以持续存在，修订了反应标准。新提出的分类反应类别包括临床完全缓解和进展性疾病。

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引用次数: 0

Modernizing multiple myeloma clinical trial eligibility to improve equity and inclusivity by hematological parameters 多发性骨髓瘤临床试验资格现代化，通过血液学参数提高公平性和包容性。

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2025-02-01 DOI: 10.1053/j.seminhematol.2024.10.008

Lauren Merz , Monique Hartley-Brown , Maureen Achebe , Craig Cole , Bindu Kanapuru , Ola Banjo , George Mulligan , Katie Wozniak , Anne Quinn Young , Hearn Jay Cho

In the United States, Black people experience multiple myeloma (MM) at a frequency that is more than double that of White people and experience much higher rates of mortality. Despite bearing a disproportionate impact of both MM incidence and mortality, Black patients are significantly underrepresented in most MM clinical trials. This is in part because Black patients experience a higher prevalence of hemoglobinopathies and Duffy-null phenotype, which affect hemoglobin and neutrophil levels, respectively, potentially excluding patients from clinical trials. The Multiple Myeloma Research Foundation (MMRF) has convened a series of Health Equity Summits that include a focus on creating inclusive clinical trials for MM. The present paper, an output of the most recent workshop, focuses on the role of laboratory reference ranges as a barrier to clinical trial participation and offers tangible steps to improve the enrollment of a diverse and representative population.

在美国，黑人患多发性骨髓瘤（MM）的频率是白人的两倍多，死亡率也高得多。尽管黑人患者在多发性骨髓瘤的发病率和死亡率方面都受到不成比例的影响，但在大多数多发性骨髓瘤临床试验中，黑人患者的比例却明显偏低。部分原因是黑人患者的血红蛋白病和达菲-无效表型发病率较高，这两种疾病分别影响血红蛋白和中性粒细胞水平，有可能将患者排除在临床试验之外。多发性骨髓瘤研究基金会（MMRF）召开了一系列 "健康公平峰会"（Health Equity Summits），其中包括重点讨论如何为多发性骨髓瘤开展包容性临床试验。本论文是最近一次研讨会的成果之一，重点讨论了实验室参考范围对临床试验参与的阻碍作用，并提出了切实可行的步骤，以改善多样化和代表性人群的入组情况。

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outside front cover, PMS 8883 metallic AND 4/C 封面外侧，PMS 8883 金属色和 4/C

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2025-02-01 DOI: 10.1053/S0037-1963(25)00004-6

引用次数: 0

FaMMily Affairs: Dissecting inherited contributions to multiple myeloma risk 家族事务：剖析遗传因素对多发性骨髓瘤风险的影响。

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2025-02-01 DOI: 10.1053/j.seminhematol.2024.11.006

Saoirse Bodnar , Tehilla Brander , Julie Gold , Ayuko Iverson , Alessandro Lagana , Kenan Onel , Sundar Jagannath , Samir Parekh , Santiago Thibaud

Etiological links to multiple myeloma (MM) remain poorly understood, though emerging evidence suggests a significant hereditary component. This review integrates current literature on inherited factors contributing to MM risk, synthesizing both epidemiologic and genomic data. We examine familial clustering patterns, assess genome-wide association studies (GWAS) that reveal common genetic variants linked to MM, and explore rare, high-penetrance variants in key susceptibility genes. Additionally, we advocate for routine germline screening in high-risk MM populations, particularly those with a strong family history of cancer, a personal history of cancer, or early-onset disease. By elucidating the inherited influences on MM predisposition, this review seeks to inform future research and refine risk assessment strategies in this population.

多发性骨髓瘤（MM）的病因学联系仍然知之甚少，尽管新出现的证据表明其具有重要的遗传成分。这篇综述整合了目前关于遗传因素导致MM风险的文献，综合了流行病学和基因组数据。我们研究了家族聚类模式，评估了揭示与MM相关的常见遗传变异的全基因组关联研究（GWAS），并探索了关键易感基因中罕见的高外显率变异。此外，我们提倡在高风险MM人群中进行常规生殖系筛查，特别是那些有强烈的癌症家族史、个人癌症史或早发性疾病的人群。通过阐明遗传因素对MM易感性的影响，本综述旨在为未来的研究提供信息，并完善该人群的风险评估策略。

引用次数: 0

At the cusp of a cure in Myeloma: Insights into pathogenesis, modeling and therapeutics 在骨髓瘤治疗的尖端：对发病机制，建模和治疗的见解

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2025-02-01 DOI: 10.1053/j.seminhematol.2025.02.002

Samir Parekh MD

引用次数: 0

The role of 1q abnormalities in multiple myeloma: Genomic insights, clinical implications, and therapeutic challenges 1q 异常在多发性骨髓瘤中的作用：基因组学见解、临床意义和治疗挑战。

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2025-02-01 DOI: 10.1053/j.seminhematol.2024.10.001

Zachary M. Avigan , Constantine S. Mitsiades , Alessandro Laganà

Chromosome 1q copy number variations, collectively termed +1q, are 1 of the most common cytogenetic abnormalities in multiple myeloma. 1q abnormalities are associated with overexpression of a high-risk gene signature promoting cell proliferation, apoptosis resistance, genomic instability, and treatment resistance, and acquisition or expansion of +1q subclones mediate disease development and relapse. While there remains significant controversy as to whether the presence of +1q is itself an independent driver of poor prognosis or is simply a marker of other high-risk features, +1q has recently been incorporated into multiple prognostic scoring models as a new high-risk cytogenetic abnormality. In this review, we present possible underlying genetic mechanisms of high-risk disease in +1q myeloma, implications for subclonal development, its role in modifying the tumor microenvironment, current evidence for clinical significance in newly-diagnosed and relapsed patients, and current controversies in +1q classification and prognostication.

染色体 1q 拷贝数变异统称为 +1q，是多发性骨髓瘤最常见的细胞遗传学异常之一。1q 异常与促进细胞增殖、抗凋亡、基因组不稳定性和抗药性的高风险基因特征的过度表达有关，而 +1q 亚克隆的获得或扩增介导了疾病的发展和复发。虽然对于+1q本身是否是不良预后的独立驱动因素或仅仅是其他高危特征的标志物仍存在很大争议，但最近+1q已作为一种新的高危细胞遗传学异常被纳入多种预后评分模型。在这篇综述中，我们将介绍+1q骨髓瘤高危疾病的可能潜在遗传机制、对亚克隆发展的影响、其在改变肿瘤微环境中的作用、目前在新诊断和复发患者中的临床意义证据，以及目前在+1q分类和预后判断中存在的争议。

引用次数: 0

Melanoma antigen genes (MAGE); novel functional targets in multiple myeloma 黑色素瘤抗原基因（MAGE）；多发性骨髓瘤的新功能靶点。

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2025-02-01 DOI: 10.1053/j.seminhematol.2024.10.007

Anna Huo-Chang Mei , Alessandro Laganà , Roman Osman , Hearn Jay Cho

Melanoma Antigen Genes (MAGE) are expressed in a broad range of cancers, including multiple myeloma. MAGE have been under investigation for more than 3 decades as targets for immune therapy, while in parallel, interrogation of their functions has revealed activities that may be particularly critical in multiple myeloma. MAGE-C1 is expressed in about 75% of newly diagnosed cases and this is maintained through the natural history of the disease. In contrast, MAGE-A3 is expressed in about 35% of newly diagnosed cases, but this increases to more than 75% after relapse. MAGE-A3 expression was associated with poor clinical outcome and resistance to chemotherapy. Translational studies have revealed that MAGE-A3 regulates cell cycling and apoptosis in myeloma cells. Genomic, gene expression, and multiomic studies demonstrate relations with high-risk subgroups of patients. MAGE-A3 mediates these functions through partnership with Kap1 to form a ubiquitin ligase complex. Structural analysis of the interaction between MAGE-A3 and Kap1 gives insight into the biochemical activity and substrate specificity and suggests novel pharmacologic strategies to inhibit them. These studies demonstrating MAGE-A3 oncogenic functions suggest that it may also be a suitable target for small molecule inhibition in multiple myeloma that may be broadly applicable to other cancers that express it.

黑色素瘤抗原基因（MAGE）在包括多发性骨髓瘤在内的多种癌症中均有表达。30 多年来，人们一直在研究 MAGE 作为免疫疗法靶点的作用，与此同时，对其功能的研究也发现了在多发性骨髓瘤中可能特别关键的活性。在新诊断的病例中，MAGE-C1 在大约 75% 的病例中表达，并在疾病的自然史中保持不变。相比之下，MAGE-A3在新诊断病例中的表达率约为35%，但在复发后会增加到75%以上。MAGE-A3 的表达与不良的临床预后和对化疗的耐药性有关。转化研究发现，MAGE-A3 可调节骨髓瘤细胞的细胞周期和凋亡。基因组、基因表达和多基因组研究表明，MAGE-A3 与高风险亚组患者有关。MAGE-A3通过与Kap1合作形成泛素连接酶复合物来介导这些功能。通过对 MAGE-A3 和 Kap1 之间相互作用的结构分析，可以深入了解它们的生化活性和底物特异性，并提出了抑制它们的新型药物策略。这些证明 MAGE-A3 致癌功能的研究表明，它也可能是多发性骨髓瘤小分子抑制剂的合适靶点，并可广泛应用于其他表达 MAGE-A3 的癌症。

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Smoldering multiple myeloma: Integrating biology and risk into management 燃烧性多发性骨髓瘤：将生物学和风险纳入管理。

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2025-02-01 DOI: 10.1053/j.seminhematol.2024.10.002

Roshani Patel , Elizabeth Hill , Madhav Dhodapkar

Smoldering multiple myeloma (SMM) was first described over 40 years ago yet much is still unknown including which patients will ultimately progress to symptomatic multiple myeloma (MM). The genetics of the premalignant clone and the immune microenvironment in which it exists is now well understood to both play a role in disease progression. However, the clinical risk models available to help identify patients at most risk of progression still rely primarily on data reflecting volume of disease rather than underlying biology. While it is of upmost importance to accurately diagnose patients with SMM to avoid over or under treatment, efforts are ongoing to tease out if early intervention is indeed warranted for a subgroup of patients with SMM. This article will review the history and biology of SMM, discuss the utility of existing risk models, and examine the efforts to date which have challenged standard management.

烟雾型多发性骨髓瘤（SMM）在 40 多年前首次被描述，但仍有许多未知因素，包括哪些患者最终会发展为有症状的多发性骨髓瘤（MM）。恶性前克隆的遗传学及其所处的免疫微环境在疾病进展中的作用现已得到充分了解。然而，现有的临床风险模型仍主要依赖于反映疾病体积的数据，而不是潜在的生物学数据，来帮助识别面临最大疾病进展风险的患者。虽然准确诊断SMM患者以避免过度治疗或治疗不足至关重要，但目前仍在努力研究是否确实需要对SMM亚组患者进行早期干预。本文将回顾SMM的历史和生物学特性，讨论现有风险模型的实用性，并研究迄今为止对标准管理提出挑战的各种努力。

引用次数: 0

Extramedullary myeloma in the era of CAR T-cell and bispecific antibody therapies CAR - t细胞和双特异性抗体治疗时代的髓外骨髓瘤。

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2025-02-01 DOI: 10.1053/j.seminhematol.2025.02.001

Larysa Sanchez, Shambavi Richard

Despite the significant advancements in multiple myeloma therapy over the last decade, current unmet needs include populations of patients who continue to have inferior outcomes, such as those with high-risk cytogenetics, elderly and frail patients, plasma cell leukemia, central nervous system involvement, and extramedullary disease. Though T-cell redirecting therapies have shown excellent efficacy in advanced multiple myeloma, the ability of these therapies to overcome high-risk disease such as extramedullary involvement in myeloma is an area of critical attention. In this review, we seek to examine the specific impact of currently available data of T-cell redirecting therapies, including approved and investigational chimeric antigen receptor T-cell and bispecific antibody therapies, on outcomes in patients with extramedullary myeloma.

尽管在过去十年中多发性骨髓瘤治疗取得了重大进展，但目前未满足的需求包括那些预后较差的患者群体，如高危细胞遗传学患者、老年人和体弱患者、浆细胞白血病、中枢神经系统受累和髓外疾病。尽管t细胞重定向疗法在晚期多发性骨髓瘤中显示出卓越的疗效，但这些疗法克服骨髓瘤髓外受累等高风险疾病的能力是一个值得关注的领域。在这篇综述中，我们试图检查目前可用的t细胞重定向治疗数据的具体影响，包括批准的和正在研究的嵌合抗原受体t细胞和双特异性抗体治疗，对髓外骨髓瘤患者的预后。

引用次数: 0

Immunocompetent mouse models of multiple myeloma 免疫功能正常的多发性骨髓瘤小鼠模型。

IF 5 3区医学 Q1 HEMATOLOGY

Seminars in hematology

Pub Date : 2025-02-01 DOI: 10.1053/j.seminhematol.2024.11.003

Peter Leif Bergsagel, Marta Chesi

Immunocompetent murine models of multiple myeloma are critical for understanding the pathogenesis of multiple myeloma and for the development of novel immunotherapeutics. Different models are available in Balb/c and C57Bl strains, each with different advantages and disadvantages. The availability of many transplantable cell lines allows for the conduct of experiments with large cohorts of mice bearing identical tumors, while cell lines that grow in vitro can be used for genetic manipulations. The introduction of human CRBN into these models allows for the study of IMiDs and cereblon based PROTACs in mice. New genetically engineered models based on germinal center cell activation of Nsd2 or Ccnd1 together with constitutive NFkB are being developed to model some of the important genetic subtypes of human multiple myeloma.

免疫功能健全的多发性骨髓瘤小鼠模型对于了解多发性骨髓瘤的发病机制和开发新型免疫疗法至关重要。Balb/c和C57Bl品系有不同的模型，各有利弊。有了许多可移植的细胞系，就可以用携带相同肿瘤的大批小鼠进行实验，而体外生长的细胞系则可用于遗传操作。在这些模型中引入人类 CRBN，可以在小鼠中研究 IMiDs 和基于脑隆的 PROTACs。目前正在开发基于生殖中心细胞激活 Nsd2 或 Ccnd1 以及组成型 NFkB 的新基因工程模型，以模拟人类多发性骨髓瘤的一些重要遗传亚型。

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Seminars in hematology

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