Pub Date : 2024-10-03DOI: 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.
{"title":"Rnf111 has a pivotal role in regulating development of definitive hematopoietic stem and progenitor cells through the Smad2/3-Gcsfr/NO axis in zebrafish.","authors":"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","doi":"10.3324/haematol.2024.285438","DOIUrl":"https://doi.org/10.3324/haematol.2024.285438","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12964,"journal":{"name":"Haematologica","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142371709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-01DOI: 10.3324/haematol.2024.285806
Guillaume P Andrieu, Vahid Asnafi
{"title":"Drive to survive: gene dependency in T-cell acute lymphoblastic leukemia.","authors":"Guillaume P Andrieu, Vahid Asnafi","doi":"10.3324/haematol.2024.285806","DOIUrl":"10.3324/haematol.2024.285806","url":null,"abstract":"","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/PMC11443407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758386","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}
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.
{"title":"A pediatric-inspired regimen for adolescent and adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia: a prospective study from China.","authors":"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","doi":"10.3324/haematol.2023.284228","DOIUrl":"10.3324/haematol.2023.284228","url":null,"abstract":"<p><p>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.</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/PMC11443404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485436","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}
Pub Date : 2024-10-01DOI: 10.3324/haematol.2024.285612
Jane Koo, Jonathan C Howell, Lindsey Hornung, Anthony Sabulski, Parinda A Mehta, Stella M Davies, Kasiani C Myers
{"title":"Infrequent fractures and resilient bone mineral density: bone health in patients with Fanconi anemia.","authors":"Jane Koo, Jonathan C Howell, Lindsey Hornung, Anthony Sabulski, Parinda A Mehta, Stella M Davies, Kasiani C Myers","doi":"10.3324/haematol.2024.285612","DOIUrl":"10.3324/haematol.2024.285612","url":null,"abstract":"","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/PMC11443388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175055","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}
Pub Date : 2024-10-01DOI: 10.3324/haematol.2023.284738
Jinjun Cheng, Liqiang Xi, Yoon Jang, Jung Kim, Hao-Wei Wang, Stefania Pittaluga, Elaine S Jaffe, Mark Raffeld
{"title":"An investigation of germline variants of <i>HAVCR2</i> in subcutaneous panniculitis-like T-cell lymphoma and related lesions in a North American population.","authors":"Jinjun Cheng, Liqiang Xi, Yoon Jang, Jung Kim, Hao-Wei Wang, Stefania Pittaluga, Elaine S Jaffe, Mark Raffeld","doi":"10.3324/haematol.2023.284738","DOIUrl":"10.3324/haematol.2023.284738","url":null,"abstract":"","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/PMC11443401/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310626","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}
Pub Date : 2024-10-01DOI: 10.3324/haematol.2024.285420
Jahanzaib Khwaja, Nicole Japzon, Maria Gabriel, Oliver Tomkins, Jindriska Lindsay, Charalampia Kyriakou, Ashutosh Wechalekar, Shirley D'Sa
{"title":"Ethnic diversity in presentation and outcome of Waldenström macroglobulinemia and IgM monoclonal gammopathy of clinical significance in the United Kingdom.","authors":"Jahanzaib Khwaja, Nicole Japzon, Maria Gabriel, Oliver Tomkins, Jindriska Lindsay, Charalampia Kyriakou, Ashutosh Wechalekar, Shirley D'Sa","doi":"10.3324/haematol.2024.285420","DOIUrl":"10.3324/haematol.2024.285420","url":null,"abstract":"","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/PMC11443397/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261262","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}
Pub Date : 2024-10-01DOI: 10.3324/haematol.2024.285043
Alexey V Danilov, Ian W Flinn, Matthew S Davids, Beth Gregory, Ohad Bentur, David Sidransky, Jennifer R Brown
{"title":"The phase III DUO trial of PI3K inhibitor duvelisib <i>versus</i> ofatumumab in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma: final analysis including overall survival.","authors":"Alexey V Danilov, Ian W Flinn, Matthew S Davids, Beth Gregory, Ohad Bentur, David Sidransky, Jennifer R Brown","doi":"10.3324/haematol.2024.285043","DOIUrl":"10.3324/haematol.2024.285043","url":null,"abstract":"","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/PMC11443371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175233","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}
Pub Date : 2024-10-01DOI: 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.
{"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}
Pub Date : 2024-10-01DOI: 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.
{"title":"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.","authors":"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","doi":"10.3324/haematol.2023.283428","DOIUrl":"10.3324/haematol.2023.283428","url":null,"abstract":"<p><p>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.</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/PMC11443366/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863938","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}
Pub Date : 2024-10-01DOI: 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.
{"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}