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Rnf111 has a pivotal role in regulating development of definitive hematopoietic stem and progenitor cells through the Smad2/3-Gcsfr/NO axis in zebrafish. 在斑马鱼中,Rnf111通过Smad2/3-Gcsfr/NO轴调控确定性造血干细胞和祖细胞的发育。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-10-03 DOI: 10.3324/haematol.2024.285438
Xiaohui Liu, Jinghan Sha, Luxiang Wang, Zixuan Wang, Zhou Fang, Xiao Han, Shuiyi Tan, Yi Chen, Hao Yuan, Hugues De The, Jun Zhou, Jun Zhu

The ubiquitination or SUMOylation of hematopoietic related factors plays pivotal roles in hematopoiesis. RNF111, known as a ubiquitin ligase (Ubl), is a newly discovered SUMO-targeted ubiquitin ligase (STUbl) involved in multiple signaling pathways mediated by TGF-β family members. However, its role in hematopoiesis remains unclear. Herein, a heritable Rnf111 mutant zebrafish line was generated by CRISPR/Cas9-mediated genome editing. Impaired hematopoietic stem and progenitor cells (HSPC) of definitive hematopoiesis was found in Rnf111 deficient mutants. Ablation of Rnf111 resulted in decreased phosphorylation of Smad2/3 in HSPC. Definitive endoderm 2 inducer (IDE2), which specifically activates TGF-β signaling and downstream Smad2 phosphorylation, can restore the definitive hematopoiesis in Rnf111-deficient embryos. Further molecular mechanism studies revealed that Gcsfr/NO signaling was an important target pathway of Smad2/3 involved in Rnf111-mediated HSPC development. In conclusion, our study demonstrated that Rnf111 contributes to the development of HSPC by maintaining Smad2/3 phosphorylation and the Gcsfr/NO signaling pathway activation. Keywords: Rnf111, Ubiquitin ligase (UbL), HSPC, Smad2/3, Gcsfr/NO.

造血相关因子的泛素化或 SUMOylation 在造血过程中发挥着关键作用。RNF111被称为泛素连接酶(Ubl),是一种新发现的SUMO靶向泛素连接酶(STUbl),参与了由TGF-β家族成员介导的多种信号通路。然而,它在造血过程中的作用仍不清楚。在此,通过 CRISPR/Cas9 介导的基因组编辑产生了遗传性 Rnf111 突变斑马鱼品系。在 Rnf111 基因缺陷突变体中发现,确定性造血的造血干细胞和祖细胞(HSPC)功能受损。Rnf111的消减导致HSPC中Smad2/3的磷酸化减少。终末内胚层2诱导剂(IDE2)可特异性激活TGF-β信号传导和下游Smad2磷酸化,从而恢复Rnf111缺陷胚胎的终末造血功能。进一步的分子机制研究发现,Gcsfr/NO信号是Smad2/3参与Rnf111介导的HSPC发育的重要靶途径。总之,我们的研究表明,Rnf111通过维持Smad2/3磷酸化和Gcsfr/NO信号通路的激活来促进HSPC的发育。关键词Rnf111 泛素连接酶(UbL) HSPC Smad2/3 Gcsfr/NO
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引用次数: 0
Drive to survive: gene dependency in T-cell acute lymphoblastic leukemia. 生存动力:T 细胞急性淋巴细胞白血病的基因依赖性。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-10-01 DOI: 10.3324/haematol.2024.285806
Guillaume P Andrieu, Vahid Asnafi
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引用次数: 0
A pediatric-inspired regimen for adolescent and adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia: a prospective study from China. 针对青少年和成人费城染色体阴性急性淋巴细胞白血病患者的儿科启发方案:一项来自中国的前瞻性研究。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-10-01 DOI: 10.3324/haematol.2023.284228
Xiaoyuan Gong, Qiuyun Fang, Runxia Gu, Shaowei Qiu, Kaiqi Liu, Dong Lin, Chunlin Zhou, Guangji Zhang, Benfa Gong, Yuntao Liu, Yan Li, Bingcheng Liu, Ying Wang, Hui Wei, Yingchang Mi, Jianxiang Wang

Several international centers have used and reported on pediatric-inspired regimens to treat adolescent and adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia (Ph- ALL). However, there is a lack of prospective data from the Chinese population. We performed a prospective study with a pediatric-inspired regimen (IH-2014 regimen) to treat adolescent and adult Ph- ALL patients in our center. From 2014 to 2021, a total of 415 patients aged between 14 and 65 years (median age, 27 years) were included in this study. After a median follow-up of 40.8 months, the 5-year overall survival, disease-free survival, and event-free survival rates were 53.8%, 51.1% and 45.0%, respectively. The regimen was generally well tolerated and safe, and the overall chemotherapy-related mortality was 3.6%. Age ≥40 years and persistent detectable minimal residual disease (MRD) after induction were independent prognostic factors. Traditional risk factors for adult patients combined with post-induction MRD had predictive significance for survival and relapse, which is helpful in the selection of subsequent treatment. Patients with high-risk factors who can achieve a deep MRD response after induction do not derive benefit from allogeneic hematopoietic stem cell transplantation.

一些国际研究中心已经对青少年和成人费城染色体阴性急性淋巴细胞白血病(Ph- ALL)患者使用并报道了儿科启发方案。然而,目前还缺乏针对中国人群的前瞻性数据。在此,我们在本中心开展了一项前瞻性研究,采用儿科启发方案(IH-2014方案)治疗青少年和成人Ph-ALL患者。从2014年到2021年,共有415名14至65岁(中位年龄27岁)的患者参与了这项研究。中位随访时间为40.8个月,5年总生存率、无病生存率和无事件生存率分别为53.8%、51.1%和45.0%。化疗方案的耐受性和安全性普遍良好,化疗相关死亡率为 3.6%。年龄≥40岁和诱导后持续存在可检测到的最小残留病(MRD)是独立的预后因素。成年患者的传统风险因素加上诱导后的 MRD 对生存和复发具有预测意义,有助于选择后续治疗。具有高风险因素的患者在诱导后可获得深度MRD反应,但并不能从异体造血干细胞移植中获益。
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引用次数: 0
Infrequent fractures and resilient bone mineral density: bone health in patients with Fanconi anemia. 不常发生骨折和有弹性的骨矿物质密度:范可尼贫血症患者的骨骼健康。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-10-01 DOI: 10.3324/haematol.2024.285612
Jane Koo, Jonathan C Howell, Lindsey Hornung, Anthony Sabulski, Parinda A Mehta, Stella M Davies, Kasiani C Myers
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引用次数: 0
An investigation of germline variants of HAVCR2 in subcutaneous panniculitis-like T-cell lymphoma and related lesions in a North American population. 对北美人群中皮下泛发性类 T 细胞淋巴瘤及相关病变中 HAVCR2 基因变异的调查。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-10-01 DOI: 10.3324/haematol.2023.284738
Jinjun Cheng, Liqiang Xi, Yoon Jang, Jung Kim, Hao-Wei Wang, Stefania Pittaluga, Elaine S Jaffe, Mark Raffeld
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引用次数: 0
Ethnic diversity in presentation and outcome of Waldenström macroglobulinemia and IgM monoclonal gammopathy of clinical significance in the United Kingdom. 英国瓦尔登斯特伦巨球蛋白血症和具有临床意义的 IgM 单克隆丙种球蛋白病在表现和预后方面的种族多样性。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-10-01 DOI: 10.3324/haematol.2024.285420
Jahanzaib Khwaja, Nicole Japzon, Maria Gabriel, Oliver Tomkins, Jindriska Lindsay, Charalampia Kyriakou, Ashutosh Wechalekar, Shirley D'Sa
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引用次数: 0
The phase III DUO trial of PI3K inhibitor duvelisib versus ofatumumab in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: final analysis including overall survival. 复发/难治性慢性淋巴细胞白血病/小淋巴细胞淋巴瘤PI3K抑制剂duvelisib与ofatumumab的III期DUO试验:包括总生存期在内的最终分析。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-10-01 DOI: 10.3324/haematol.2024.285043
Alexey V Danilov, Ian W Flinn, Matthew S Davids, Beth Gregory, Ohad Bentur, David Sidransky, Jennifer R Brown
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引用次数: 0
Cell-free DNA from nail clippings as source of normal control for genomic studies in hematologic malignancies. 将指甲剪中的无细胞 DNA 作为血液恶性肿瘤基因组研究的正常对照源。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-10-01 DOI: 10.3324/haematol.2024.285054
Melissa Krystel-Whittemore, Kseniya Petrova-Drus, Ryan N Ptashkin, Mark D Ewalt, JinJuan Yao, Ying Liu, Menglei Zhu, Jamal Benhamida, Benjamin Durham, Jyoti Kumar, Khedoudja Nafa, Iwona Kiecka, Anita S Bowman, Erika Gedvilaite, Jacklyn Casanova, Yun-Te Lin, Abhinita S Mohanty, Satshil Rana, Anoop Balakrishnan Rema, Ivelise Rijo, Nelio Chaves, Paulo Salazar, Anita Yun, Sean Lachhander, Wei Wang, Mohammad S Haque, Wenbin Xiao, Mikhail Roshal, Sergio Giralt, Gilles Salles, Raajit Rampal, Eytan M Stein, Miguel-Angel Perales, Steven Horwitz, Ann Jakubowski, Doris Ponce, Alina Markova, Ozge Birsoy, Diana Mandelker, Simon Mantha, Ahmet Dogan, Ryma Benayed, Marc Ladanyi, Michael F Berger, A Rose Brannon, Ahmet Zehir, Chad Vanderbilt, Maria E Arcila

Comprehensive genomic sequencing is becoming a critical component in the assessment of hematologic malignancies, with broad implications for patients' management. In this context, unequivocally discriminating somatic from germline events is challenging but greatly facilitated by matched analysis of tumor:normal pairs of samples. In contrast to solid tumors, in hematologic malignancies conventional sources of normal control material (peripheral blood, buccal swabs, saliva) could be highly involved by the neoplastic process, rendering them unsuitable. In this work we describe our real-world experience using cell-free DNA (cfDNA) isolated from nail clippings as an alternate source of normal control material, through the dedicated review of 2,610 tumor:nail pairs comprehensively sequenced by MSK-IMPACT-heme. Overall, we found that nail cfDNA is a robust germline control for paired genomic studies. In a subset of patients, nail DNA may be contaminated by tumor DNA, reflecting unique attributes of the hematologic disease and transplant history. Contamination is generally low level, but significantly more common among patients with myeloid neoplasms (20.5%; 304/1,482) than among those with lymphoid diseases (5.4%; 61/1,128) and particularly enriched in myeloproliferative neoplasms with marked myelofibrosis. When identified in patients with lymphoid and plasma-cell neoplasms, mutations commonly reflected a myeloid profile and correlated with a concurrent/evolving clonal myeloid neoplasm. Donor DNA was identified in 22% (11/50) of nails collected after allogeneic stem-cell transplantation. In this cohort, an association with a recent history of graft-versus-host disease was identified. These findings should be considered as a potential limitation to the use of nails as a source of normal control DNA but could also provide important diagnostic information regarding the disease process.

全面基因组测序正成为血液系统恶性肿瘤评估的关键组成部分,对患者管理具有广泛影响。在这种情况下,明确区分体细胞事件和种系事件具有挑战性,但通过对肿瘤:正常人配对进行匹配分析则可大大简化这一工作。与实体瘤相比,传统的正常对照来源(外周血、口腔拭子、唾液)可能会受到肿瘤过程的高度影响,因此并不适用。在这项工作中,我们介绍了通过 MSK-IMPACT-heme 对 2610 对肿瘤:指甲进行全面测序,使用从指甲剪中分离的游离细胞 DNA(cfDNA)作为正常对照的替代来源的实际经验。总体而言,我们发现指甲 cfDNA 是配对基因组研究的强大种系控制源。在一部分患者中,指甲DNA可能会受到肿瘤DNA的污染,这反映了血液病和移植史的独特属性。污染程度一般较低,但与淋巴疾病(5.4%;61/1128)相比,骨髓肿瘤患者(20.5%;304/1482)的污染程度明显更高,尤其是在骨髓纤维化明显的骨髓增生性肿瘤中。当在淋巴细胞和浆细胞肿瘤患者中发现突变时,突变通常反映了髓细胞的特征,并与并发/发展中的克隆性髓细胞肿瘤相关。在同种异体干细胞移植后采集的指甲中,22%(11/50)的指甲中发现了供体 DNA。在这个队列中,发现了与近期移植物抗宿主疾病相关的病史。这些发现应被视为使用指甲作为正常对照的潜在限制,但也可提供有关疾病过程的重要诊断信息。
{"title":"Cell-free DNA from nail clippings as source of normal control for genomic studies in hematologic malignancies.","authors":"Melissa Krystel-Whittemore, Kseniya Petrova-Drus, Ryan N Ptashkin, Mark D Ewalt, JinJuan Yao, Ying Liu, Menglei Zhu, Jamal Benhamida, Benjamin Durham, Jyoti Kumar, Khedoudja Nafa, Iwona Kiecka, Anita S Bowman, Erika Gedvilaite, Jacklyn Casanova, Yun-Te Lin, Abhinita S Mohanty, Satshil Rana, Anoop Balakrishnan Rema, Ivelise Rijo, Nelio Chaves, Paulo Salazar, Anita Yun, Sean Lachhander, Wei Wang, Mohammad S Haque, Wenbin Xiao, Mikhail Roshal, Sergio Giralt, Gilles Salles, Raajit Rampal, Eytan M Stein, Miguel-Angel Perales, Steven Horwitz, Ann Jakubowski, Doris Ponce, Alina Markova, Ozge Birsoy, Diana Mandelker, Simon Mantha, Ahmet Dogan, Ryma Benayed, Marc Ladanyi, Michael F Berger, A Rose Brannon, Ahmet Zehir, Chad Vanderbilt, Maria E Arcila","doi":"10.3324/haematol.2024.285054","DOIUrl":"10.3324/haematol.2024.285054","url":null,"abstract":"<p><p>Comprehensive genomic sequencing is becoming a critical component in the assessment of hematologic malignancies, with broad implications for patients' management. In this context, unequivocally discriminating somatic from germline events is challenging but greatly facilitated by matched analysis of tumor:normal pairs of samples. In contrast to solid tumors, in hematologic malignancies conventional sources of normal control material (peripheral blood, buccal swabs, saliva) could be highly involved by the neoplastic process, rendering them unsuitable. In this work we describe our real-world experience using cell-free DNA (cfDNA) isolated from nail clippings as an alternate source of normal control material, through the dedicated review of 2,610 tumor:nail pairs comprehensively sequenced by MSK-IMPACT-heme. Overall, we found that nail cfDNA is a robust germline control for paired genomic studies. In a subset of patients, nail DNA may be contaminated by tumor DNA, reflecting unique attributes of the hematologic disease and transplant history. Contamination is generally low level, but significantly more common among patients with myeloid neoplasms (20.5%; 304/1,482) than among those with lymphoid diseases (5.4%; 61/1,128) and particularly enriched in myeloproliferative neoplasms with marked myelofibrosis. When identified in patients with lymphoid and plasma-cell neoplasms, mutations commonly reflected a myeloid profile and correlated with a concurrent/evolving clonal myeloid neoplasm. Donor DNA was identified in 22% (11/50) of nails collected after allogeneic stem-cell transplantation. In this cohort, an association with a recent history of graft-versus-host disease was identified. These findings should be considered as a potential limitation to the use of nails as a source of normal control DNA but could also provide important diagnostic information regarding the disease process.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140049289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Treatment of chronic-phase chronic myeloid leukemia in patients randomized to dasatinib or imatinib after suboptimal responses to 3 months of imatinib therapy: final 5-year results from DASCERN. 对三个月伊马替尼治疗反应不理想的慢性期慢性髓性白血病患者随机使用达沙替尼或伊马替尼的治疗:DASCERN 的最终五年结果。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-10-01 DOI: 10.3324/haematol.2023.283428
Jorge E Cortes, Qian Jiang, Jianxiang Wang, Jianyu Weng, Huanling Zhu, Xiaoli Liu, Andreas Hochhaus, Dong-Wook Kim, Jerald Radich, Michael Savona, Patricia Martin-Regueira, Oumar Sy, Giuseppe Saglio

Early molecular response at 3 months is predictive of improved overall survival and progression-free survival in patients with chronic myeloid leukemia in the chronic phase. Although about one-third of patients treated with first-line imatinib do not achieve an early molecular response, long-term overall survival and progression-free survival are still observed in most patients. DASCERN (NCT01593254) is a prospective, phase IIb, randomized trial evaluating a switch to dasatinib in patients who have not achieved an early molecular response after 3 months of treatment with first-line imatinib. Early analysis demonstrated an improved major molecular response (MMR) rate at 12 months with dasatinib versus imatinib (29% vs. 13%, P=0.005). Here, we report results from the final 5-year follow-up. In total, 174 patients were randomized to dasatinib and 86 to remain on imatinib. Forty-six (53%) patients who remained on imatinib but subsequently experienced failure were allowed to cross over to dasatinib per protocol. At a minimum follow-up of 60 months, the cumulative MMR rate was significantly higher in patients randomized to dasatinib than those randomized to imatinib (77% vs. 44%, P<0.001). The median time to MMR was 13.9 months with dasatinib versus 19.7 months with imatinib. The safety profile was consistent with previous reports. These results demonstrate that switching to dasatinib after a suboptimal response to imatinib at 3 months leads to faster MMR, provides earlier deep molecular responses, and improves some outcomes in patients with chronic myeloid leukemia in the chronic phase.

3个月的早期分子反应(EMR)可预测慢性髓性白血病慢性期(CML-CP)患者总生存期(OS)和无进展生存期(PFS)的改善。虽然约有三分之一接受伊马替尼一线治疗的患者没有达到EMR,但大多数患者仍能观察到长期OS和PFS。DASCERN(NCT01593254)是一项前瞻性 IIb 期随机试验,评估了在接受伊马替尼一线治疗 3 个月后仍未达到 EMR 的患者转用达沙替尼的情况。早期分析显示,与伊马替尼相比,达沙替尼治疗12个月后的主要分子反应(MMR)率有所提高(29% vs. 13%,P=0.005)。在此,我们报告最后5年的随访结果。共有 174 名患者随机接受达沙替尼治疗,86 名患者继续接受伊马替尼治疗。46名(53%)继续服用伊马替尼但随后出现治疗失败的患者被允许按照方案转为服用达沙替尼。在至少 60 个月的随访中,随机接受达沙替尼治疗的患者的累积 MMR 率明显高于接受伊马替尼治疗的患者(77% 对 44%,P<0.05)。
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引用次数: 0
Checkpoint inhibition enhances cell contacts between CD4+ T cells and Hodgkin-Reed-Sternberg cells of classic Hodgkin lymphoma. 检查点抑制增强了 CD4+ T 细胞与典型霍奇金淋巴瘤的霍奇金-里德-斯登伯格细胞之间的细胞接触。
IF 8.2 1区 医学 Q1 HEMATOLOGY Pub Date : 2024-10-01 DOI: 10.3324/haematol.2023.284512
Kübra Yadigaroglu, Sonja Scharf, Steffen Gretser, Hendrik Schäfer, Aresu Sadeghi Shoreh Deli, Andreas G Loth, Hasmik Yegoryan, Roland Schmitz, Emmanuel Donnadieu, Martin-Leo Hansmann, Sylvia Hartmann

Although checkpoint molecules like CTLA-4 and PD1 have been described several years ago, checkpoint inhibitors such as nivolumab (an anti-PD-1 antibody) have only recently been used to treat classic Hodgkin lymphoma (cHL). Several studies have shown convincing therapeutic effects of nivolumab in cHL. However, the mechanism of action of nivolumab in cHL is not fully understood. The aim of this study was to monitor changes in cell motility and cell contacts after administration of nivolumab to an in vitro model of cHL as well as to native hyperplastic lymphoid tissue and native human tissue from cHL. In both tissue and in vitro, CD4+, CD8+, CD30+ and CD20+ cell velocities were unchanged after nivolumab incubation. In contrast, in primary cHL tissue, the duration of cell contacts between CD4+ T cells and Hodgkin-Reed-Sternberg cells was significantly increased after 5 hours of nivolumab treatment, and the number of contacts with HRS cells was also slightly increased for CD4+ T cells (not significant), suggesting that CD4+ T cells in particular contribute to the cytotoxicity observed as a result of nivolumab therapy. There was no change in the duration of cell contacts in the hyperplastic lymphoid tissue after nivolumab incubation. In conclusion, we show here for the first time by imaging of native lymphoma tissue an enhanced interaction of CD4+ T cells and Hodgkin-Reed-Sternberg cells in cHL after nivolumab administration.

虽然 CTLA-4 和 PD1 等检查点分子早在几年前就已被描述,但 Nivolumab(一种抗 PD-1 抗体)等检查点抑制剂直到最近才被用于治疗典型的霍奇金淋巴瘤(cHL)。多项研究表明,Nivolumab 对 cHL 具有令人信服的治疗效果。然而,Nivolumab在cHL中的作用机制尚未完全明了。本研究的目的是在体外 cHL 模型、原生增生淋巴组织和 cHL 原生人体组织中使用 Nivolumab 后,监测细胞运动和细胞接触的变化。在组织和体外模型中,CD4+、CD8+、CD30+和CD20+细胞速度在Nivolumab孵育后均保持不变。相反,在原发性 cHL 组织中,CD4+ T 细胞与 HRS 细胞接触的持续时间在 Nivolumab 治疗 5 小时后显著增加,CD4+ T 细胞与 HRS 细胞接触的次数也略有增加(不显著),这表明 CD4+ T 细胞尤其有助于 Nivolumab 治疗后观察到的细胞毒性。Nivolumab孵育后,增生淋巴组织中细胞接触的持续时间没有变化。总之,我们在这里首次通过对原生淋巴瘤组织的成像显示,在服用 Nivolumab 后,CD4+ T 细胞与 cHL 中 HRS 细胞的相互作用增强了。
{"title":"Checkpoint inhibition enhances cell contacts between CD4<sup>+</sup> T cells and Hodgkin-Reed-Sternberg cells of classic Hodgkin lymphoma.","authors":"Kübra Yadigaroglu, Sonja Scharf, Steffen Gretser, Hendrik Schäfer, Aresu Sadeghi Shoreh Deli, Andreas G Loth, Hasmik Yegoryan, Roland Schmitz, Emmanuel Donnadieu, Martin-Leo Hansmann, Sylvia Hartmann","doi":"10.3324/haematol.2023.284512","DOIUrl":"10.3324/haematol.2023.284512","url":null,"abstract":"<p><p>Although checkpoint molecules like CTLA-4 and PD1 have been described several years ago, checkpoint inhibitors such as nivolumab (an anti-PD-1 antibody) have only recently been used to treat classic Hodgkin lymphoma (cHL). Several studies have shown convincing therapeutic effects of nivolumab in cHL. However, the mechanism of action of nivolumab in cHL is not fully understood. The aim of this study was to monitor changes in cell motility and cell contacts after administration of nivolumab to an in vitro model of cHL as well as to native hyperplastic lymphoid tissue and native human tissue from cHL. In both tissue and in vitro, CD4+, CD8+, CD30+ and CD20+ cell velocities were unchanged after nivolumab incubation. In contrast, in primary cHL tissue, the duration of cell contacts between CD4+ T cells and Hodgkin-Reed-Sternberg cells was significantly increased after 5 hours of nivolumab treatment, and the number of contacts with HRS cells was also slightly increased for CD4+ T cells (not significant), suggesting that CD4+ T cells in particular contribute to the cytotoxicity observed as a result of nivolumab therapy. There was no change in the duration of cell contacts in the hyperplastic lymphoid tissue after nivolumab incubation. In conclusion, we show here for the first time by imaging of native lymphoma tissue an enhanced interaction of CD4+ T cells and Hodgkin-Reed-Sternberg cells in cHL after nivolumab administration.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11443406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141080531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
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