Leukemia最新文献

筛选
英文 中文
Essential role of Dhx16-mediated ribosome assembly in maintenance of hematopoietic stem cells Dhx16 介导的核糖体组装在造血干细胞的维持中发挥重要作用
IF 12.8 1区 医学
Leukemia Pub Date : 2024-09-27 DOI: 10.1038/s41375-024-02423-3
Zhigang Li, Jiankun Fan, Yalan Xiao, Wei Wang, Changlin Zhen, Junbing Pan, Weiru Wu, Yuanyuan Liu, Zhe Chen, Qinrong Yan, Hanqing Zeng, Shuyu Luo, Lun Liu, Zhanhan Tu, Xueya Zhao, Yu Hou
{"title":"Essential role of Dhx16-mediated ribosome assembly in maintenance of hematopoietic stem cells","authors":"Zhigang Li, Jiankun Fan, Yalan Xiao, Wei Wang, Changlin Zhen, Junbing Pan, Weiru Wu, Yuanyuan Liu, Zhe Chen, Qinrong Yan, Hanqing Zeng, Shuyu Luo, Lun Liu, Zhanhan Tu, Xueya Zhao, Yu Hou","doi":"10.1038/s41375-024-02423-3","DOIUrl":"10.1038/s41375-024-02423-3","url":null,"abstract":"Hematopoietic stem cells (HSCs) are vital for the differentiation of all mature blood cells, with their homeostasis being tightly regulated by intrinsic and extrinsic factors. Alternative splicing, mediated by the spliceosome complex, plays a crucial role in regulating HSC homeostasis by increasing protein diversity. This study focuses on the ATP-dependent RNA helicase DHX16, a key spliceosome component, and its role in HSC regulation. Using conditional knockout mice, we demonstrate that loss of Dhx16 in the hematopoietic system results in significant depletion of hematopoietic stem and progenitor cells, bone marrow failure, and rapid mortality. Dhx16-deficient HSCs exhibit impaired quiescence, G2-M phase cell cycle arrest, reduced protein synthesis, abnormal ribosome assembly, increased apoptosis, and decreased self-renewal capacity. Multi-omics analysis identified intron 4 retention in Emg1 mRNA in Dhx16 knockout HSCs, leading to reduced EMG1 protein expression, disrupted ribosome assembly, and nucleolar stress, activating the p53 pathway. Overexpression of Emg1 in Dhx16-deficient HSCs partially restored ribosome assembly and HSC function, suggesting Emg1 as a potential therapeutic target for ribosomopathies. Our findings reveal the critical role of Dhx16 in HSC homeostasis through the regulation of alternative splicing and ribosome assembly, providing insights into the molecular mechanisms underlying hematopoietic diseases and potential therapeutic strategies.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"38 12","pages":"2699-2708"},"PeriodicalIF":12.8,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142325543","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}
引用次数: 0
Prognostic value of response to first-line hydroxyurea according to IPSET stratification in essential thrombocythemia 根据 IPSET 分层对原发性血小板增多症患者一线羟基脲反应的预后价值
IF 12.8 1区 医学
Leukemia Pub Date : 2024-09-27 DOI: 10.1038/s41375-024-02416-2
Marta Santaliestra, Marta Garrote, María Soledad Noya, Manuel Pérez-Encinas, Alicia Senín, Raúl Pérez-López, Francisca Ferrer-Marín, Gonzalo Carreño-Tarragona, Gonzalo Caballero, Elena Magro, Patricia Vélez, Miguel Ángel Cortés Vázquez, Ana Moretó, Anna Angona, Irene Pastor-Galán, José María Guerra, Carmen García Hernández, María Isabel Mata, Ruth Stuckey, María Teresa Gómez-Casares, Laura Fox, Beatriz Cuevas, Valentín García-Gutiérrez, Ana Triguero, Eduardo Arellano-Rodrigo, Juan Carlos Hernández-Boluda, Alberto Alvarez-Larrán
{"title":"Prognostic value of response to first-line hydroxyurea according to IPSET stratification in essential thrombocythemia","authors":"Marta Santaliestra, Marta Garrote, María Soledad Noya, Manuel Pérez-Encinas, Alicia Senín, Raúl Pérez-López, Francisca Ferrer-Marín, Gonzalo Carreño-Tarragona, Gonzalo Caballero, Elena Magro, Patricia Vélez, Miguel Ángel Cortés Vázquez, Ana Moretó, Anna Angona, Irene Pastor-Galán, José María Guerra, Carmen García Hernández, María Isabel Mata, Ruth Stuckey, María Teresa Gómez-Casares, Laura Fox, Beatriz Cuevas, Valentín García-Gutiérrez, Ana Triguero, Eduardo Arellano-Rodrigo, Juan Carlos Hernández-Boluda, Alberto Alvarez-Larrán","doi":"10.1038/s41375-024-02416-2","DOIUrl":"10.1038/s41375-024-02416-2","url":null,"abstract":"Hydroxyurea (HU) constitutes the first-line treatment in most patients with essential thrombocythemia (ET), but criteria for changing therapy are not clearly established. The prognostic value of complete hematological response (CHR) and resistance/intolerance to HU was assessed in 1080 patients from the Spanish Registry of ET, classified according to revised IPSET-Thrombosis stratification (Very low- n = 61, Low- n = 83, Intermediate- n = 261, and High-risk n = 675). With a median therapy duration of 5 years, CHR was registered in 720 (67%) patients (1-year probability 51%) and resistance/intolerance in 219 (20%) patients (5-years probability 13%). After correction by other risk factors, High-risk patients achieving CHR showed a reduced risk of arterial thrombosis (HR: 0.35, 95%CI: 0.2–0.6, p = 0.001) and a trend towards lower risk of venous thrombosis (HR: 0.45, 95%CI: 0.2–1.02, p = 0.06) whereas no association was observed for intermediate- or low-risk patients. In comparison with non-responders, intermediate- and high-risk patients achieving CHR had longer survival and lower myelofibrosis incidence. Development of resistance/intolerance to HU, mainly cytopenia, was associated with higher probability of myelofibrosis but no effect on survival or thrombotic risk was demonstrated. In conclusion, CHR with HU is associated with better outcomes and might be an early indicator for selecting candidates to second-line clinical trials.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"38 12","pages":"2636-2643"},"PeriodicalIF":12.8,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02416-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328771","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
Can PROTACs cure Leukemia? PROTACs 能治愈白血病吗?
IF 12.8 1区 医学
Leukemia Pub Date : 2024-09-26 DOI: 10.1038/s41375-024-02427-z
Kathleen M. Sakamoto
{"title":"Can PROTACs cure Leukemia?","authors":"Kathleen M. Sakamoto","doi":"10.1038/s41375-024-02427-z","DOIUrl":"10.1038/s41375-024-02427-z","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"38 12","pages":"2552-2553"},"PeriodicalIF":12.8,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02427-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321376","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
New criteria for estimating numbers of CD34-positive cells in a graft needed for posttransplant bone marrow recovery 估计移植后骨髓恢复所需的移植物中 CD34 阳性细胞数量的新标准
IF 12.8 1区 医学
Leukemia Pub Date : 2024-09-25 DOI: 10.1038/s41375-024-02424-2
Yahui Feng, Saibing Qi, Yu Hu, Wen Yan, Yanping Ji, Mingyang Wang, Xiaowen Gong, Qiujin Shen, Wei Zhang, Huilan Liu, Xianjing Zhang, Mengyun Chen, Erling Chen, Xiaolin Zhai, Yi He, Donglin Yang, Aiming Pang, Mingzhe Han, Robert Peter Gale, Zimin Sun, Erlie Jiang, Junren Chen
{"title":"New criteria for estimating numbers of CD34-positive cells in a graft needed for posttransplant bone marrow recovery","authors":"Yahui Feng, Saibing Qi, Yu Hu, Wen Yan, Yanping Ji, Mingyang Wang, Xiaowen Gong, Qiujin Shen, Wei Zhang, Huilan Liu, Xianjing Zhang, Mengyun Chen, Erling Chen, Xiaolin Zhai, Yi He, Donglin Yang, Aiming Pang, Mingzhe Han, Robert Peter Gale, Zimin Sun, Erlie Jiang, Junren Chen","doi":"10.1038/s41375-024-02424-2","DOIUrl":"10.1038/s41375-024-02424-2","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"38 12","pages":"2735-2738"},"PeriodicalIF":12.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02424-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321385","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
Epcoritamab in relapsed/refractory large B-cell lymphoma: 2-year follow-up from the pivotal EPCORE NHL-1 trial 埃博瑞他单抗治疗复发/难治性大B细胞淋巴瘤:EPCORE NHL-1关键试验的两年随访结果
IF 12.8 1区 医学
Leukemia Pub Date : 2024-09-25 DOI: 10.1038/s41375-024-02410-8
Catherine Thieblemont, Yasmin H. Karimi, Herve Ghesquieres, Chan Y. Cheah, Michael Roost Clausen, David Cunningham, Wojciech Jurczak, Young Rok Do, Robin Gasiorowski, David John Lewis, Tae Min Kim, Marjolein van der Poel, Michelle Limei Poon, Tatyana Feldman, Kim M. Linton, Anna Sureda, Martin Hutchings, Minh H. Dinh, Nurgul Kilavuz, David Soong, Thomas Mark, Mariana Sacchi, Tycel Phillips, Pieternella J. Lugtenburg
{"title":"Epcoritamab in relapsed/refractory large B-cell lymphoma: 2-year follow-up from the pivotal EPCORE NHL-1 trial","authors":"Catherine Thieblemont, Yasmin H. Karimi, Herve Ghesquieres, Chan Y. Cheah, Michael Roost Clausen, David Cunningham, Wojciech Jurczak, Young Rok Do, Robin Gasiorowski, David John Lewis, Tae Min Kim, Marjolein van der Poel, Michelle Limei Poon, Tatyana Feldman, Kim M. Linton, Anna Sureda, Martin Hutchings, Minh H. Dinh, Nurgul Kilavuz, David Soong, Thomas Mark, Mariana Sacchi, Tycel Phillips, Pieternella J. Lugtenburg","doi":"10.1038/s41375-024-02410-8","DOIUrl":"10.1038/s41375-024-02410-8","url":null,"abstract":"Primary results (median follow-up, 10.7 months) from the pivotal EPCORE® NHL-1 study in relapsed or refractory (R/R) large B-cell lymphoma (LBCL) demonstrated deep, durable responses with epcoritamab, a CD3xCD20 bispecific antibody, when used as monotherapy. We report long-term efficacy and safety results in patients with LBCL (N = 157; 25.1-month median follow-up). As of April 21, 2023, overall response rate was 63.1% and complete response (CR) rate was 40.1%. Estimated 24-month progression-free survival (PFS) and overall survival (OS) rates were 27.8% and 44.6%, respectively. An estimated 64.2% of complete responders remained in CR at 24 months. Estimated 24-month PFS and OS rates among complete responders were 65.1% and 78.2%, respectively. Of 119 minimal residual disease (MRD)-evaluable patients, 45.4% had MRD negativity, which correlated with longer PFS and OS. CR rates were generally consistent across predefined subgroups: 36% prior chimeric antigen receptor (CAR) T-cell therapy, 32% primary refractory disease, and 37% International Prognostic Index ≥3. The most common treatment-emergent adverse events were cytokine release syndrome (51.0%), pyrexia (24.8%), fatigue (24.2%), and neutropenia (23.6%). These results underscore the long-term benefit of epcoritamab for treating R/R LBCL with deep responses across subgroups, including patients with hard-to-treat disease and expected poor prognosis (ClinicalTrials.gov Registration: NCT03625037).","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"38 12","pages":"2653-2662"},"PeriodicalIF":12.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02410-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317198","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
Pola-R-CHP or R-CHOEP for first-line therapy of younger patients with high-risk diffuse large B-cell lymphoma: a retrospective comparison of two randomized phase 3 trials Pola-R-CHP或R-CHOEP用于年轻高危弥漫大B细胞淋巴瘤患者的一线治疗:两项随机三期试验的回顾性比较
IF 12.8 1区 医学
Leukemia Pub Date : 2024-09-25 DOI: 10.1038/s41375-024-02420-6
Georg Lenz, Hervé Tilly, Marita Ziepert, Bettina Altmann, Charles Herbaux, Fabian Frontzek, Maike Nickelsen, Calvin Lee, Jamie Hirata, Deniz Sahin, Saibah Chohan, Connie Lee Batlevi, Mark Yan, Franck Morschhauser, Norbert Schmitz
{"title":"Pola-R-CHP or R-CHOEP for first-line therapy of younger patients with high-risk diffuse large B-cell lymphoma: a retrospective comparison of two randomized phase 3 trials","authors":"Georg Lenz, Hervé Tilly, Marita Ziepert, Bettina Altmann, Charles Herbaux, Fabian Frontzek, Maike Nickelsen, Calvin Lee, Jamie Hirata, Deniz Sahin, Saibah Chohan, Connie Lee Batlevi, Mark Yan, Franck Morschhauser, Norbert Schmitz","doi":"10.1038/s41375-024-02420-6","DOIUrl":"10.1038/s41375-024-02420-6","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"38 12","pages":"2709-2711"},"PeriodicalIF":12.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02420-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142321320","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
Longitudinal follow up of a phase 2 trial of venetoclax added to hyper-CVAD, nelarabine and pegylated asparaginase in patients with T-cell acute lymphoblastic leukemia and lymphoma 对T细胞急性淋巴细胞白血病和淋巴瘤患者进行的Venetoclax加入超CVAD、奈拉滨和聚乙二醇天冬酰胺酶的2期试验的纵向随访
IF 12.8 1区 医学
Leukemia Pub Date : 2024-09-25 DOI: 10.1038/s41375-024-02414-4
Farhad Ravandi, Jayastu Senapati, Nitin Jain, Nicholas J. Short, Tapan Kadia, Gautam Borthakur, Marina Konopleva, William Wierda, Xuelin Huang, Abhishek Maiti, Ghayas Issa, Hayley Balkin, Rebecca Garris, Alessandra Ferrajoli, Guillermo Garcia-Manero, Yesid Alvarado, Partow Kebriaei, Elias Jabbour, Hagop M. Kantarjian
{"title":"Longitudinal follow up of a phase 2 trial of venetoclax added to hyper-CVAD, nelarabine and pegylated asparaginase in patients with T-cell acute lymphoblastic leukemia and lymphoma","authors":"Farhad Ravandi, Jayastu Senapati, Nitin Jain, Nicholas J. Short, Tapan Kadia, Gautam Borthakur, Marina Konopleva, William Wierda, Xuelin Huang, Abhishek Maiti, Ghayas Issa, Hayley Balkin, Rebecca Garris, Alessandra Ferrajoli, Guillermo Garcia-Manero, Yesid Alvarado, Partow Kebriaei, Elias Jabbour, Hagop M. Kantarjian","doi":"10.1038/s41375-024-02414-4","DOIUrl":"10.1038/s41375-024-02414-4","url":null,"abstract":"Optimal frontline use of active agents in T-cell acute lymphoblastic leukemia/lymphoma (T-ALL/LBL) is prudent to improve outcomes. We report the long-term follow-up of the phase 2 trial of HyperCVAD with nelarabine and pegylated asparaginase (Original cohort). In the latest protocol iteration venetoclax was added to the induction/consolidation regimen (Venetoclax cohort). Eligible patients were adults with untreated T-ALL/LBL or after minimal therapy and with adequate organ function. Primary endpoint of this analysis was improvement in 2-year progression free survival (PFS) and overall survival (OS) with venetoclax. From Aug 2007 to Dec 2024, 145 patients, at a median age of 35.4 years, were treated; 46 (33.8%) were in the venetoclax cohort. At median follow-up (mFU) of 62.4 months, 5-year PFS, duration of response (DOR), and OS were 63.7%, 72.0% and 66.2% respectively. In the venetoclax cohort (mFU 24.4 months) 2-year PFS (87.9% versus 64.1%, p = 0.03) and 2-year DOR (93.6% versus 69.2%, p = 0.005) were superior to the original cohort (mFU 89.4 months) and 2-year OS appeared better (87.8% versus 73.9%, p = 0.16). Febrile neutropenia was the most common serious adverse event, seen in 60% patients. The addition of venetoclax to HyperCVAD-nelarabine-pegylated asparaginase was tolerable and led to improvement in DOR and PFS.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"38 12","pages":"2717-2721"},"PeriodicalIF":12.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317196","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}
引用次数: 0
LocoMMotion: a study of real-life current standards of care in triple-class exposed patients with relapsed/refractory multiple myeloma – 2-year follow-up (final analysis) LocoMMotion:针对复发性/难治性多发性骨髓瘤三类暴露患者的现实生活中现行护理标准研究--2 年随访(最终分析)
IF 12.8 1区 医学
Leukemia Pub Date : 2024-09-25 DOI: 10.1038/s41375-024-02404-6
María-Victoria Mateos, Katja Weisel, Valerio De Stefano, Hartmut Goldschmidt, Michel Delforge, Mohamad Mohty, Dominik Dytfeld, Emanuele Angelucci, Laure Vincent, Aurore Perrot, Reuben Benjamin, Niels W. C. J. van de Donk, Enrique M. Ocio, Tito Roccia, Jordan M. Schecter, Silva Koskinen, Imène Haddad, Vadim Strulev, Lada Mitchell, Jozefien Buyze, Octavio Costa Filho, Hermann Einsele, Philippe Moreau
{"title":"LocoMMotion: a study of real-life current standards of care in triple-class exposed patients with relapsed/refractory multiple myeloma – 2-year follow-up (final analysis)","authors":"María-Victoria Mateos, Katja Weisel, Valerio De Stefano, Hartmut Goldschmidt, Michel Delforge, Mohamad Mohty, Dominik Dytfeld, Emanuele Angelucci, Laure Vincent, Aurore Perrot, Reuben Benjamin, Niels W. C. J. van de Donk, Enrique M. Ocio, Tito Roccia, Jordan M. Schecter, Silva Koskinen, Imène Haddad, Vadim Strulev, Lada Mitchell, Jozefien Buyze, Octavio Costa Filho, Hermann Einsele, Philippe Moreau","doi":"10.1038/s41375-024-02404-6","DOIUrl":"10.1038/s41375-024-02404-6","url":null,"abstract":"Treatment of relapsed/refractory multiple myeloma (RRMM) is challenging as patients exhaust all available therapies and the disease becomes refractory to standard drug classes. Here we report the final results of LocoMMotion, the first prospective study of real-world clinical practice (RWCP) in triple-class exposed (TCE) patients with RRMM, with a median follow-up of 26.4 months (range, 0.1–35.0). Patients (N  =  248) had received median 4 prior LOT (range, 2–13) at enrollment. 91 unique regimens were used in index LOT. Overall response rate was 31.9% (95% CI, 26.1–38.0), median progression-free survival (PFS) was 4.6 months (95% CI, 3.9–5.6) and median overall survival was 13.8 months (95% CI, 10.8–17.0). 152 patients (61.3%) had subsequent LOTs with 134 unique regimens, of which 78 were used in first subsequent LOT. Median PFS2 (from start of study through first subsequent LOT) was 10.8 months (95% CI, 8.4–13.0). 158 patients died on study, 67.7% due to progressive disease. Additional subgroup analyses and long-term safety summaries are reported. The high number of RWCP treatment regimens utilized and poor clinical outcomes confirm a lack of standardized treatment for TCE patients with RRMM, highlighting the need for new treatments with novel mechanisms.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"38 12","pages":"2554-2560"},"PeriodicalIF":12.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02404-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317199","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
MERTK inhibition selectively activates a DC – T-cell axis to provide anti-leukemia immunity 抑制 MERTK 可选择性地激活 DC - T 细胞轴,从而提供抗白血病免疫力
IF 12.8 1区 医学
Leukemia Pub Date : 2024-09-25 DOI: 10.1038/s41375-024-02408-2
Justus M. Huelse, Swati S. Bhasin, Kristen M. Jacobsen, Juhye Yim, Beena E. Thomas, Gianna M. Branella, Mojtaba Bakhtiari, Madison L. Chimenti, Travon A. Baxter, Sunil S. Raikar, Xiaodong Wang, Stephen V. Frye, Curtis J. Henry, H. Shelton Earp, Manoj Bhasin, Deborah DeRyckere, Douglas K. Graham
{"title":"MERTK inhibition selectively activates a DC – T-cell axis to provide anti-leukemia immunity","authors":"Justus M. Huelse, Swati S. Bhasin, Kristen M. Jacobsen, Juhye Yim, Beena E. Thomas, Gianna M. Branella, Mojtaba Bakhtiari, Madison L. Chimenti, Travon A. Baxter, Sunil S. Raikar, Xiaodong Wang, Stephen V. Frye, Curtis J. Henry, H. Shelton Earp, Manoj Bhasin, Deborah DeRyckere, Douglas K. Graham","doi":"10.1038/s41375-024-02408-2","DOIUrl":"10.1038/s41375-024-02408-2","url":null,"abstract":"TAM-family tyrosine kinases (TYRO3, AXL and MERTK) are potential cancer therapeutic targets. In previous studies MERTK inhibition in the immune microenvironment was therapeutically effective in a B-cell acute leukemia (B-ALL) model. Here, we probed anti-leukemia immune mechanisms and evaluated roles for TYRO3 and AXL in the leukemia microenvironment. Host Mertk knock-out or MERTK inhibitor MRX-2843 increased CD8α+ dendritic cells (DCs) with enhanced antigen-presentation capacity in the leukemia microenvironment and inhibited leukemogenesis. High MERTK or low DC gene expression were associated with poor prognosis in pediatric ALL patients, indicating the clinical relevance of these findings. MRX-2843 increased CD8+ T-cell numbers and prevented induction of exhaustion markers, implicating a DC – T-cell axis. Indeed, combined depletion of CD8α+ DCs and CD8+ T-cells was required to abrogate anti-leukemia immunity in Mertk–/– mice. Tyro3–/– mice were also protected against B-ALL, implicating TYRO3 as an immunotherapeutic target. In contrast to Mertk–/– mice, Tyro3–/– did not increase CD8α+ DCs with enhanced antigen-presentation capacity and therapeutic activity was less dependent on DCs, indicating a different immune mechanism. Axl–/– did not impact leukemogenesis. These data demonstrate differential TAM kinase roles in the leukemia microenvironment and provide rationale for development of MERTK and/or TYRO3-targeted immunotherapies.","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"38 12","pages":"2685-2698"},"PeriodicalIF":12.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317197","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}
引用次数: 0
PVR (CD155) epigenetic status mediates immunotherapy response in multiple myeloma PVR(CD155)的表观遗传学状态介导多发性骨髓瘤的免疫疗法反应
IF 12.8 1区 医学
Leukemia Pub Date : 2024-09-24 DOI: 10.1038/s41375-024-02419-z
Laura Martinez-Verbo, Yoana Veselinova, Pere Llinàs-Arias, Carlos A. García-Prieto, Aleix Noguera-Castells, Miguel L. Pato, Alberto Bueno-Costa, Ignacio Campillo-Marcos, Lorea Villanueva, Aina Oliver-Caldes, Oriol Cardus, Sergi V. Salsench, Almudena García-Ortiz, Antonio Valeri, Elizabeta A. Rojas, Naroa Barrena, Norma C. Gutiérrez, Felipe Prósper, Xabier Agirre, Carlos Fernández de Larrea, Joaquín Martínez-López, Gerardo Ferrer, Manel Esteller
{"title":"PVR (CD155) epigenetic status mediates immunotherapy response in multiple myeloma","authors":"Laura Martinez-Verbo, Yoana Veselinova, Pere Llinàs-Arias, Carlos A. García-Prieto, Aleix Noguera-Castells, Miguel L. Pato, Alberto Bueno-Costa, Ignacio Campillo-Marcos, Lorea Villanueva, Aina Oliver-Caldes, Oriol Cardus, Sergi V. Salsench, Almudena García-Ortiz, Antonio Valeri, Elizabeta A. Rojas, Naroa Barrena, Norma C. Gutiérrez, Felipe Prósper, Xabier Agirre, Carlos Fernández de Larrea, Joaquín Martínez-López, Gerardo Ferrer, Manel Esteller","doi":"10.1038/s41375-024-02419-z","DOIUrl":"10.1038/s41375-024-02419-z","url":null,"abstract":"","PeriodicalId":18109,"journal":{"name":"Leukemia","volume":"38 12","pages":"2722-2726"},"PeriodicalIF":12.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41375-024-02419-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142317241","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
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信