Seminars in hematology最新文献_第6页

The complexities of T-cell dysfunction in chronic lymphocytic leukemia 慢性淋巴细胞白血病中 T 细胞功能障碍的复杂性。

IF 5 3区医学

Seminars in hematology Pub Date : 2024-06-01 DOI: 10.1053/j.seminhematol.2024.04.001

Elena Camerini , Derk Amsen , Arnon P. Kater , Fleur S. Peters

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Metabolic reprogramming in the CLL TME; potential for new therapeutic targets CLL TME 中的代谢重编程；新治疗靶点的潜力

IF 5 3区医学

Seminars in hematology Pub Date : 2024-06-01 DOI: 10.1053/j.seminhematol.2024.02.001

Helga Simon-Molas , Chiara Montironi , Anna Kabanova , Eric Eldering

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B-cell receptor immunoglobulin stereotypy in chronic lymphocytic leukemia: Key to understanding disease biology and stratifying patients 慢性淋巴细胞白血病的 B 细胞受体免疫球蛋白定型：了解疾病生物学和对患者进行分层的关键

IF 3.6 3区医学

Seminars in hematology Pub Date : 2024-04-01 DOI: 10.1053/j.seminhematol.2023.12.005

Andreas Agathangelidis , Thomas Chatzikonstantinou , Kostas Stamatopoulos

{"title":"B-cell receptor immunoglobulin stereotypy in chronic lymphocytic leukemia: Key to understanding disease biology and stratifying patients","authors":"Andreas Agathangelidis , Thomas Chatzikonstantinou , Kostas Stamatopoulos","doi":"10.1053/j.seminhematol.2023.12.005","DOIUrl":"10.1053/j.seminhematol.2023.12.005","url":null,"abstract":"<div><p><span>Sequence convergence, otherwise stereotypy, of B-cell receptor immunoglobulin (BcR IG) from unrelated patients is a distinctive feature of the IG gene repertoire in chronic lymphocytic leukemia<span> (CLL) whereby patients expressing a particular BcR IG archetype are classified into groups termed stereotyped subsets. From a biological perspective, the fact that a considerable fraction (∼41%) of patients with CLL express (quasi)identical or stereotyped BcR IG underscores the key role of antigen selection in the natural history of CLL. From a clinical perspective, at odds with the pronounced heterogeneity of CLL at large, patients belonging to the same stereotyped subset display consistent clinical presentation and outcome, including response to treatment, likely as a reflection of consistent biological background. Many major stereotyped subsets were recently shown to have satellites, that is, smaller subsets that are immunogenetically similar. Preliminary evidence supports that this similarity extends to shared biological and even clinical features, with important implications for patient stratification. Consequently, BcR IG stereotypy emerges as a powerful tool for dissecting the heterogeneity of CLL toward refined </span></span>risk stratification and, eventually, more precise therapeutic interventions.</p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 2","pages":"Pages 91-99"},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139054602","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

Targeting the B cell receptor signaling pathway in chronic lymphocytic leukemia 靶向慢性淋巴细胞白血病中的 B 细胞受体信号通路

IF 3.6 3区医学

Seminars in hematology Pub Date : 2024-04-01 DOI: 10.1053/j.seminhematol.2024.04.002

John T. Patton, Jennifer A. Woyach

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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 3.6 3区医学

Seminars in hematology Pub Date : 2024-04-01 DOI: 10.1053/S0037-1963(24)00062-3

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Vaccinations in patients with chronic lymphocytic leukemia 慢性淋巴细胞白血病患者的疫苗接种

IF 3.6 3区医学

Seminars in hematology Pub Date : 2024-04-01 DOI: 10.1053/j.seminhematol.2024.01.003

Elizabeth R. Francis , Jennifer Vu , Catherine Ostos Perez , Clare Sun

引用次数: 0

Therapeutic targeting of apoptosis in chronic lymphocytic leukemia 针对慢性淋巴细胞白血病细胞凋亡的治疗方法

IF 3.6 3区医学

Seminars in hematology Pub Date : 2024-04-01 DOI: 10.1053/j.seminhematol.2024.01.015

Inhye E. Ahn, Matthew S. Davids

{"title":"Therapeutic targeting of apoptosis in chronic lymphocytic leukemia","authors":"Inhye E. Ahn, Matthew S. Davids","doi":"10.1053/j.seminhematol.2024.01.015","DOIUrl":"10.1053/j.seminhematol.2024.01.015","url":null,"abstract":"<div><p>Therapeutic targeting of apoptosis with small molecule B-cell lymphoma 2 (BCL-2) inhibition with venetoclax is highly efficacious in CLL, leading to sustained deep responses, particularly among patients with treatment-naïve disease with favorable prognostic markers. Patients with unfavorable genetic characteristics such as <em>TP53</em> aberration and unmutated IGHV may also derive durable benefits, but their remission duration after time-limited venetoclax-containing combination therapy is shorter, particularly in patients with relapsed/refractory disease. Emerging data indicate that the context of disease progression after initial treatment with venetoclax may define the success of re-treatment with venetoclax. Specifically, continuous venetoclax exposure may select for resistant disease due to genetic mechanisms such as <em>BCL2</em> mutations and functional resistance mechanisms such as hyperphosphorylation of BCL-2 family proteins, which decrease the affinity of venetoclax binding to the target or lead to increased MCL-1 dependence and concomitant decrease in BCL-2 dependence. These patients may be best served by switching to a different class of targeted agents at the time of progression. In contrast, relapsed CLL that arises while being off therapy after a period of time-limited venetoclax-based regimens maintains sensitivity to re-treatment with venetoclax for the majority of patients. Novel strategies related to therapeutic targeting of apoptosis include next-generation BCL-2 inhibitors with improved potency and pharmacokinetic profiles, direct targeting of anti-apoptotic BH3 family proteins beyond BCL-2 such as MCL-1, and indirect targeting of MCL-1 through mechanisms such as small molecule cyclin-dependent kinase 9 inhibitors.</p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 2","pages":"Pages 109-118"},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139831525","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

Prognostication in chronic lymphocytic leukemia 慢性淋巴细胞白血病的预后

IF 3.6 3区医学

Seminars in hematology Pub Date : 2024-04-01 DOI: 10.1053/j.seminhematol.2024.02.002

Riccardo Moia, Gianluca Gaidano

{"title":"Prognostication in chronic lymphocytic leukemia","authors":"Riccardo Moia, Gianluca Gaidano","doi":"10.1053/j.seminhematol.2024.02.002","DOIUrl":"10.1053/j.seminhematol.2024.02.002","url":null,"abstract":"<div><p>Chronic lymphocytic leukemia (CLL) is the most common type of leukemia in Western countries. CLL is a highly heterogeneous disease: some patients may never require therapy and others relapse several times after different therapeutic strategies. Therefore, in CLL, prognostic markers are essential to capture high-risk patients for different clinical endpoints including early treatment requirement, early progression after BTK or BCL2 inhibitors and Richter transformation. In early stage CLL, different biological and clinical biomarkers have been identified to predict time to treatment requirement that could be used to identify the most appropriate population for early intervention clinical trial. However, at the moment, the standard of care for early stage CLL remains watch & wait since no survival benefit has been identified in clinical trials with chemoimmunotherapy and with BTK inhibitors. In patients requiring treatment <em>TP53</em> disruptions identify high-risk patients who benefit the most from long-term continuous therapy with BTKi. On the opposite side of the spectrum, IGHV mutated patients devoid of <em>TP53</em> disruption benefit the most from fixed-duration therapy with venetoclax-obinutuzumab. In between, the highly heterogenous subgroup of patients with IGHV unmutated genes represents the group in which further efforts are needed to identify additional prognostic biomarkers aimed at selecting patients who can benefit from fixed-duration and patients who can benefit from long term BTKi therapy. In the context of the aggressive transformation of CLL, namely Richter syndrome, the clonal relationship to the CLL counterpart represents the strongest prognostic biomarker. Clonally related Richter syndrome still represents an unmet clinical need which requires further efforts to identify new therapeutic strategies.</p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 2","pages":"Pages 83-90"},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0037196324000386/pdfft?md5=b6d513be92a17e8615a4b2dc5cef6458&pid=1-s2.0-S0037196324000386-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140057523","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

Special issue on chronic lymphocytic leukemia: Prognostication and therapeutic options introductory editorial 慢性淋巴细胞白血病特刊：预后与治疗方案序言社论

IF 3.6 3区医学

Seminars in hematology Pub Date : 2024-04-01 DOI: 10.1053/j.seminhematol.2024.03.002

Barbara Eichhorst , Elisa ten Hacken

引用次数: 0

The molecular map of CLL and Richter's syndrome CLL 和里希特综合征的分子图谱

IF 3.6 3区医学

Seminars in hematology Pub Date : 2024-04-01 DOI: 10.1053/j.seminhematol.2024.01.009

Amit Sud , Erin M. Parry , Catherine J. Wu

{"title":"The molecular map of CLL and Richter's syndrome","authors":"Amit Sud , Erin M. Parry , Catherine J. Wu","doi":"10.1053/j.seminhematol.2024.01.009","DOIUrl":"10.1053/j.seminhematol.2024.01.009","url":null,"abstract":"<div><p>Clonal expansion of B-cells, from the early stages of monoclonal B-cell lymphocytosis through to chronic lymphocytic leukemia (CLL), and then in some cases to Richter's syndrome (RS) provides a comprehensive model of cancer evolution, notable for the marked morphological transformation and distinct clinical phenotypes. High-throughput sequencing of large cohorts of patients and single-cell studies have generated a molecular map of CLL and more recently, of RS, yielding fundamental insights into these diseases and of clonal evolution. A selection of CLL driver genes have been functionally interrogated to yield novel insights into the biology of CLL. Such findings have the potential to impact patient care through risk stratification, treatment selection and drug discovery. However, this molecular map remains incomplete, with extant questions concerning the origin of the B-cell clone, the role of the TME, inter- and intra-compartmental heterogeneity and of therapeutic resistance mechanisms. Through the application of multi-modal single-cell technologies across tissues, disease states and clinical contexts, these questions can now be addressed with the answers holding great promise of generating translatable knowledge to improve patient care.</p></div>","PeriodicalId":21684,"journal":{"name":"Seminars in hematology","volume":"61 2","pages":"Pages 73-82"},"PeriodicalIF":3.6,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S003719632400009X/pdfft?md5=e6b68a13a1d84b6cd8bb87a533d2c797&pid=1-s2.0-S003719632400009X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139584477","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