Experimental Hematology & Oncology最新文献

{"title":"Targeting hepcidin in colorectal cancer triggers a TNF-dependent-gasdermin E-driven immunogenic cell death response.","authors":"Antonio Di Grazia, Eleonora Franzè, Rachele Frascatani, Federica Laudisi, Teresa Pacifico, Lorenzo Tomassini, Davide Di Fusco, Vincenzo Formica, Giuseppe Sica, Carmine Stolfi, Ivan Monteleone, Giovanni Monteleone","doi":"10.1186/s40164-024-00562-y","DOIUrl":"https://doi.org/10.1186/s40164-024-00562-y","url":null,"abstract":"<p><p>Interactions between colorectal cancer (CRC) cells and the noncancerous cells in the tumor microenvironment (TME) induce mechanisms for the escape of tumor cells from immune attack. Hepcidin, a peptide that controls immune cell functions, is overproduced by CRC cells. This study aimed to evaluate whether hepcidin acts as a regulator of anti-tumor immunity in CRC. Hepcidin silencing in CRC cells was followed by enhanced TNF-driven caspase-dependent cleavage of GSDM E and death. Mice engrafted with hepcidin-deficient CT26 cells developed fewer and smaller tumors than control mice as a result of the action of tumor-infiltrating CD8+ T lymphocytes and were protected from the development of tumors in a vaccination model and exhibited long-lasting tumor protection. Additionally, hepcidin deficiency enhanced the response of mice bearing CT26-derived tumors to anti-PD-1 therapy. These results suggest that targeting hepcidin in CRC cells enhances the production of TNF thereby triggering a caspase/GSDM E-driven lytic cell death with the downstream effect of boosting a robust immune response against tumor antigens.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"95"},"PeriodicalIF":9.4,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11437719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344272","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}

{"title":"Comprehensive antitumor immune response boosted by dual inhibition of SUMOylation and MEK in MYC-expressing KRAS-mutant cancers.","authors":"Hiroshi Kotani, Tomoyoshi Yamano, Justin C Boucher, Shigeki Sato, Hiroyuki Sakaguchi, Koji Fukuda, Akihiro Nishiyama, Kaname Yamashita, Koushiro Ohtsubo, Shinji Takeuchi, Takumi Nishiuchi, Hiroko Oshima, Masanobu Oshima, Marco L Davila, Seiji Yano","doi":"10.1186/s40164-024-00563-x","DOIUrl":"https://doi.org/10.1186/s40164-024-00563-x","url":null,"abstract":"<p><p>Precision medicine has drastically changed cancer treatment strategies including KRAS-mutant cancers which have been undruggable for decades. While intrinsic or acquired treatment resistance remains unresolved in many cases, epigenome-targeted therapy may be an option to overcome. We recently discovered the effectiveness of blocking small ubiquitin-like modifier (SUMO) signaling cascade (SUMOylation) in MYC-expressing KRAS-mutant cancer cells using a SUMO-activating enzyme E inhibitor TAK-981 that results in SUMOylation inhibition. Interestingly, TAK-981 promoted the degradation of MYC via the ubiquitin-proteasome system. Moreover, combination therapy with TAK-981 and MEK inhibitor trametinib remarkably regressed xenografted KRAS-mutant tumors by accumulating DNA damage and inducing apoptosis. Whereas our recent study revealed immune-independent antitumor efficacy, we evaluated the immune responses of cancer cells and immune cells in this study. We found that TAK-981-induced MYC downregulation promoted the activation of STING followed by Stat1 and MHC class I in KRAS-mutant cancer cells. Activation of dendritic cells or T cells treated with TAK-981 was also verified by upregulated activation markers in dendritic cells or skew-toward effector-like phenotypes in T cells. Furthermore, the enhanced immune-dependent antitumor efficacy of the combination therapy with TAK-981 and trametinib was confirmed by infiltration of immune cells into tumor tissues and immunodepleting-test using immunodepleting antibodies in syngeneic immunocompetent mouse models. Together with our recent study and here, the findings support that combination inhibition of SUMOylation and MEK comprehensively conquers MYC-expressing KRAS-mutant cancers by both immune-dependent and immune-independent antitumor responses.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"94"},"PeriodicalIF":9.4,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11438268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142344371","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}

{"title":"Correction: Efficacy of NKG2D CAR-T cells with IL-15/IL-15Rα signaling for treating Epstein-Barr virus-associated lymphoproliferative disorder","authors":"Qiusui Mai, Bailin He, Shikai Deng, Qing Zeng, Yanwen Xu, Cong Wang, Yunyi Pang, Sheng Zhang, Jinfeng Li, Jinfeng Zeng, Liqin Huang, Yongshui Fu, Chengyao Li, Tingting Li, Xiaojun Xu, Ling Zhang","doi":"10.1186/s40164-024-00559-7","DOIUrl":"https://doi.org/10.1186/s40164-024-00559-7","url":null,"abstract":"&lt;p&gt;&lt;b&gt;Correction: Experimental Hematology &amp; Oncology (2024) 13:85&lt;/b&gt; &lt;b&gt;https://doi.org/10.1186/s40164-024-00553-z&lt;/b&gt;&lt;/p&gt;&lt;p&gt;In this article [1], authors Qiusui Mai, Bailin He and Shikai Deng should have been denoted as equally contributing authors. The equal contribution information was inadvertently omitted during the production process.&lt;/p&gt;&lt;p&gt;The original article has been corrected.&lt;/p&gt;&lt;ol data-track-component=\"outbound reference\" data-track-context=\"references section\"&gt;&lt;li data-counter=\"1.\"&gt;&lt;p&gt;Mai Q, He B, Deng S, Zeng Q, Xu Y, Wang C, Pang Y, Zhang S, Li J, Zeng J, Huang L, Fu Y, Li C, Li T, Xu X, Zhang L. Efficacy of NKG2D CAR-T cells with IL-15/IL-15Rα signaling for treating Epstein-Barr virus-associated lymphoproliferative disorder. Exp Hematol Oncol. 2024;13:85. https://doi.org/10.1186/s40164-024-00553-z.&lt;/p&gt;&lt;p&gt;Article CAS PubMed PubMed Central Google Scholar &lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;p&gt;Download references&lt;svg aria-hidden=\"true\" focusable=\"false\" height=\"16\" role=\"img\" width=\"16\"&gt;&lt;use xlink:href=\"#icon-eds-i-download-medium\" xmlns:xlink=\"http://www.w3.org/1999/xlink\"&gt;&lt;/use&gt;&lt;/svg&gt;&lt;/p&gt;&lt;span&gt;Author notes&lt;/span&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;Qiusui Mai, Bailin He and Shikai Deng contributed eqaully to this work.&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;h3&gt;Authors and Affiliations&lt;/h3&gt;&lt;ol&gt;&lt;li&gt;&lt;p&gt;Department of Blood Transfusion, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, 518107, China&lt;/p&gt;&lt;p&gt;Qiusui Mai &amp; Xiaojun Xu&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Transfusion Medicine, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China&lt;/p&gt;&lt;p&gt;Qiusui Mai, Shikai Deng, Qing Zeng, Cong Wang, Chengyao Li, Tingting Li &amp; Ling Zhang&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China&lt;/p&gt;&lt;p&gt;Bailin He&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Obstetrics, He Xian Memorial Affiliated Hospital of Southern Medical University, Guangzhou, 511402, China&lt;/p&gt;&lt;p&gt;Yanwen Xu&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Guangzhou Bai Rui Kang (BRK) Biological Science and Technology Limited Company, Guangzhou, 510555, China&lt;/p&gt;&lt;p&gt;Cong Wang &amp; Chengyao Li&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Department of Obstetrics, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China&lt;/p&gt;&lt;p&gt;Yunyi Pang&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Shenzhen Bao’an District Central Blood Station, Shenzhen, 518101, China&lt;/p&gt;&lt;p&gt;Sheng Zhang, Jinfeng Li &amp; Tingting Li&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Shenzhen Blood Center, Shenzhen, 518035, China&lt;/p&gt;&lt;p&gt;Jinfeng Zeng &amp; Liqin Huang&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;p&gt;Guangzhou Blood Center, Guangzhou, 510095, China&lt;/p&gt;&lt;p&gt;Yongshui Fu&lt;/p&gt;&lt;/li&gt;&lt;/ol&gt;&lt;span&gt;Authors&lt;/span&gt;&lt;ol&gt;&lt;li&gt;&lt;span&gt;Qiusui Mai&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Bailin He&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;Google Scholar&lt;/span&gt;&lt;/p&gt;&lt;/li&gt;&lt;li&gt;&lt;span&gt;Shikai Deng&lt;/span&gt;View author publications&lt;p&gt;You can also search for this author in &lt;span&gt;PubMed&lt;span&gt; &lt;/span&gt;G","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"108 1","pages":""},"PeriodicalIF":10.9,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142177915","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}

{"title":"Identifying ADGRG1 as a specific marker for tumor-reactive T cells in acute myeloid leukemia.","authors":"Yihan Mei, Yu Liu, Wenbing Liu, Manling Chen, Xiaoyu Liu, Shangshang Wang, Junli Mou, Haiyan Xing, Kejing Tang, Zheng Tian, Qing Rao, Min Wang, Runxia Gu, Shaowei Qiu, Jianxiang Wang","doi":"10.1186/s40164-024-00560-0","DOIUrl":"10.1186/s40164-024-00560-0","url":null,"abstract":"<p><p>Besides chemotherapy and hematopoietic stem cell transplantation (HSCT), autologous T cells can also serve as a new treatment approach for AML patients. However, the features of tumor-reactive T cells and their distinctive markers still lack full description. To evaluate the characteristics of tumor-reactive T cells, we collected bone marrow (BM) T cells from newly diagnosed AML patients with RUNX1::RUNX1T1 as examples for paired single-cell RNA sequencing and single-cell V(D)J sequencing. Based on the STARTRAC-like algorithm, we defined bystander T cells and tumor-reactive T cells. Compared with bystander T cells, tumor-reactive T cells presented as senescent-like cytotoxic terminally differentiated T cells (Temra) with upregulated NK-related markers. Additionally, we found ADGRG1 could serve as the specific marker of CD8⁺ T tumor-reactive T cell and validated it through the Runx1^Runx1t1/+; Mx1-Cre mouse model. In chimeric antigen receptor (CAR)-T and target cell system, ADGRG1 was selectively upregulated upon antigen-TCR encounter. Moreover, ADGRG1⁺CD8⁺ T cells released a higher level of IFN-γ and showed higher cell-killing ability when exposed to matched AML blasts. Together, our findings depict the single-cell profile of tumor-reactive T cells in AML BM and propose that ADGRG1 can act as an indicator of T cell tumor reactivity in AML, which may be further harnessed for adoptive cell therapy and tumor-reactive TCR enrichment.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"92"},"PeriodicalIF":9.4,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11380426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142145483","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}

{"title":"Ubiquitin modification in the regulation of tumor immunotherapy resistance mechanisms and potential therapeutic targets.","authors":"Zihang Hong, Furong Liu, Zhanguo Zhang","doi":"10.1186/s40164-024-00552-0","DOIUrl":"10.1186/s40164-024-00552-0","url":null,"abstract":"<p><p>Although immune checkpoint-based cancer immunotherapy has shown significant efficacy in various cancers, resistance still limits its therapeutic effects. Ubiquitination modification is a mechanism that adds different types of ubiquitin chains to proteins, mediating protein degradation or altering their function, thereby affecting cellular signal transduction. Increasing evidence suggests that ubiquitination modification plays a crucial role in regulating the mechanisms of resistance to cancer immunotherapy. Drugs targeting ubiquitination modification pathways have been shown to inhibit tumor progression or enhance the efficacy of cancer immunotherapy. This review elaborates on the mechanisms by which tumor cells, immune cells, and the tumor microenvironment mediate resistance to cancer immunotherapy and the details of how ubiquitination modification regulates these mechanisms, providing a foundation for enhancing the efficacy of cancer immunotherapy by intervening in ubiquitination modification.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"91"},"PeriodicalIF":9.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11367865/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142119349","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}

{"title":"Polyunsaturated fatty acids promote M2-like TAM deposition via dampening RhoA-YAP1 signaling in the ovarian cancer microenvironment.","authors":"Huogang Wang, Mingo Mh Yung, Yang Xuan, Fushun Chen, Waisun Chan, Michelle Ky Siu, Runying Long, Shuo Jia, Yonghao Liang, Dakang Xu, Zhangfa Song, Stephen Kw Tsui, Hextan Ys Ngan, Karen Kl Chan, David W Chan","doi":"10.1186/s40164-024-00558-8","DOIUrl":"10.1186/s40164-024-00558-8","url":null,"abstract":"<p><strong>Background: </strong>Peritoneal metastases frequently occur in epithelial ovarian cancer (EOC), resulting in poor prognosis and survival rates. Tumor-associated-macrophages (TAMs) massively infiltrate into ascites spheroids and are multi-polarized as protumoral M2-like phenotype, orchestrating the immunosuppression and promoting tumor progression. However, the impact of omental conditioned medium/ascites (OCM/AS) on TAM polarization and its function in tumor progression remains elusive.</p><p><strong>Methods: </strong>The distribution and polarization of TAMs in primary and omental metastatic EOC patients' tumors and ascites were examined by m-IHC, FACS analysis, and immunofluorescence. QPCR, immunofluorescence, FACS analysis, lipid staining assay, ROS assay, and Seahorse real-time cell metabolic assay characterized TAMs as being polarized in the ascites microenvironment. The oncogenic role of TAMs in tumor cells was demonstrated by co-cultured migration/invasion, proliferation, and spheroid formation assays. Mechanistic studies of the regulations of TAM polarization were performed by using RNA-Seq, GTPase pull-down, G-LISA activation assays, and other biochemical assays. A Yap1 macrophages (MФs) conditional knockout (cKO) mouse model demonstrated the roles of YAP1 in TAM polarization status and its pro-metastatic function. Finally, the anti-metastatic potential of targeting TAMs through restoring YAP1 by pharmacological agonist XMU MP1 was demonstrated in vitro and in vivo.</p><p><strong>Results: </strong>Abundant polyunsaturated fatty acids (PUFAs) in OCM/AS suppressed RhoA-GTPase activities, which, in turn, downregulated nuclear YAP1 in MФs, leading to increased protumoral TAM polarization accompanied by elevated OXPHOS metabolism. Abolishment of YAP1 in MФs further confirmed that a higher M2/M1 ratio of TAM polarization could alleviate CD8⁺ T cell infiltration and cytotoxicity in vivo. Consistently, the loss of YAP1 has been observed in EOC metastatic tissues, suggesting its clinical relevance. On the contrary, restoration of YAP1 expression by pharmaceutical inhibition of MST1/2 induced conversion of M2-to-M1-like polarized MФs, elevating the infiltration of CD8⁺ T cells and attenuating tumor growth.</p><p><strong>Conclusion: </strong>This study revealed that PUFAs-enriched OCM/AS of EOC promotes M2-like TAM polarization through RhoA-YAP1 inhibition, where YAP1 downregulation is required for accelerating protumoral M2-like TAM polarization, thereby causing immunosuppression and enhancing tumor progression. Conversion of M2-to-M1-like polarized MФs through Yap1 activation inhibits tumor progression and contributes to developing potential TAMs-targeted immunotherapies in combating EOC peritoneal metastases.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"90"},"PeriodicalIF":9.4,"publicationDate":"2024-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11360340/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092567","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}

{"title":"Genetic factors, risk prediction and AI application of thrombotic diseases.","authors":"Rong Wang, Liang V Tang, Yu Hu","doi":"10.1186/s40164-024-00555-x","DOIUrl":"10.1186/s40164-024-00555-x","url":null,"abstract":"<p><p>In thrombotic diseases, coagulation, anticoagulation, and fibrinolysis are three key physiological processes that interact to maintain blood in an appropriate state within blood vessels. When these processes become imbalanced, such as excessive coagulation or reduced anticoagulant function, it can lead to the formation of blood clots. Genetic factors play a significant role in the onset of thrombotic diseases and exhibit regional and ethnic variations. The decision of whether to initiate prophylactic anticoagulant therapy is a matter that clinicians must carefully consider, leading to the development of various thrombotic risk assessment scales in clinical practice. Given the considerable heterogeneity in clinical diagnosis and treatment, researchers are exploring the application of artificial intelligence in medicine, including disease prediction, diagnosis, treatment, prevention, and patient management. This paper reviews the research progress on various genetic factors involved in thrombotic diseases, analyzes the advantages and disadvantages of commonly used thrombotic risk assessment scales and the characteristics of ideal scoring scales, and explores the application of artificial intelligence in the medical field, along with its future prospects.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"89"},"PeriodicalIF":9.4,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11348605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142079762","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}

{"title":"Application patterns and outcomes of hematopoietic stem cell transplantation in peripheral T-cell lymphoma patients: a multicenter real-world study in China.","authors":"Hongye Gao, Zhuoxin Zhang, Jiali Wang, Yannan Jia, Yawei Zheng, Xiaolei Pei, Weihua Zhai, Rongli Zhang, Xin Chen, Qiaoling Ma, Jialin Wei, Donglin Yang, Aiming Pang, Yi He, Sizhou Feng, Hao Zhang, Xin Du, Xianmin Song, Yao Liu, Dehui Zou, Erlie Jiang","doi":"10.1186/s40164-024-00557-9","DOIUrl":"10.1186/s40164-024-00557-9","url":null,"abstract":"<p><p>The optimal timing and type of hematopoietic stem cell transplantation (HSCT) for treating peripheral T-cell lymphoma (PTCL) remain controversial. This retrospective real-world study investigated the application pattern and outcomes of HSCT in China. The analysis encompassed 408 PTCL patients with a median age of 45.5 years, all of whom received initial adequate therapy at five hospitals. Among patients with nodal PTCL who responded effectively to first-line therapy (the \"responders\", n = 127) and subsequently underwent HSCT consolidation (n = 47, 37.0%), 93.6% received auto-HSCT, while 6.4% underwent allo-HSCT. Front-line auto-HSCT showed potential for long-term disease control in nodal PTCL responders. Among non-nodal PTCL responders (n = 80) with HSCT (n = 26, 32.5%), 46.2% underwent allo-HSCT and 53.8% received auto-HSCT. Upfront allo-HSCT provides longer progression-free survival (PFS) for non-nodal PTCL responders, with lower 3-year cumulative incidence of relapse (CIR) (16.7% vs. 56.0%) and comparable non-relapse mortality (NRM) (10.4% vs. 11.0%) compared to auto-HSCT. For patients who achieved remission with second-line salvage regimens, allo-HSCT was the primary choice (82.4%) for non-nodal PTCL, while auto-HSCT was more common (82.4%) in nodal PTCL. Nodal PTCL patients underwent auto-HSCT after ≥ 3 lines of treatment had a higher 3-year CIR (81.0%) compared to those treated in the first (26.0%) or second line (26.0%). Non-nodal PTCL patients underwent allo-HSCT after ≥ 3 lines had a higher 3-year NRM (37.5%) compared to after first (10.4%) or second line treatment (8.5%). These findings highlight distinct HSCT application patterns for PTCL in China, emphasizing the impact of early disease control and upfront consolidative HSCT.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"88"},"PeriodicalIF":9.4,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11344441/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055223","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}

{"title":"Current and future therapies for follicular lymphoma.","authors":"Pier Luigi Zinzani, Javier Muñoz, Judith Trotman","doi":"10.1186/s40164-024-00551-1","DOIUrl":"10.1186/s40164-024-00551-1","url":null,"abstract":"<p><p>Follicular lymphoma (FL) is an indolent, germinal center B cell-derived lymphoid neoplasm, for which recent advances in treatment have substantially improved patient survival. However, FL remains an incurable and heterogeneous disease, with groups of patients experiencing early disease progression, histologic transformation, or a high risk of treatment-related toxicity. Additionally, FL is a continually relapsing disease, and response rates and disease-control intervals decrease with each subsequent line of therapy. In this review, we explore the current treatment landscape for relapsed or refractory FL and promising therapies in development, highlighting the efficacy and potential risks of each treatment. We provide a real-world perspective on the unmet needs of patients with FL. Novel therapeutic approaches in development offer a wide array of options for clinicians when treating relapsed or refractory FL. A nuanced approach is required to address the needs of individual patients, taking into consideration both the risks and benefits of each treatment option, as well as patient preferences.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"87"},"PeriodicalIF":9.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11340193/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035632","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}

{"title":"Epigenetic alterations of TP53INP1 by EHMT2 regulate the cell cycle in gastric cancer.","authors":"Tae Young Ryu, In Hwan Tae, Tae-Su Han, Jinkwon Lee, Kwangho Kim, Yunsang Kang, Solbi Kim, Hyo Jin Lee, Cho-Rok Jung, Jung Hwa Lim, Dae-Soo Kim, Mi-Young Son, Hyun-Soo Cho","doi":"10.1186/s40164-024-00554-y","DOIUrl":"10.1186/s40164-024-00554-y","url":null,"abstract":"<p><strong>Background: </strong>Gastric cancer (GC) is a type of cancer with high incidence and mortality rates. Although various chemical interventions are being developed to treat gastric cancer, there is a constant demand for research into new GC treatment targets and modes of action (MOAs) because of the low effectiveness and side effects of current treatments.</p><p><strong>Methods: </strong>Using the TCGA data portal, we identified EHMT2 overexpression in GC samples. Using RNA-seq and EHMT2-specific siRNA, we investigated the role of EHMT2 in GC cell proliferation and validated its function with two EHMT2-specific inhibitors. Through the application of 3D spheroid culture, patient-derived gastric cancer organoids (PDOs), and an in vivo model, we confirmed the role of EHMT2 in GC cell proliferation.</p><p><strong>Results: </strong>In this study, we found that EHMT2, a histone 3 lysine 9 (H3K9) methyltransferase, is significantly overexpressed in GC patients compared with healthy individuals. Knockdown of EHMT2 with siRNA induced G1 cell cycle arrest and attenuated GC cell proliferation. Furthermore, we confirmed that TP53INP1 induction by EHMT2 knockdown induced cell cycle arrest and inhibited GC cell proliferation. Moreover, specific EHMT2 inhibitors, BIX01294 and UNC0638, induced cell cycle arrest in GC cell lines through TP53INP1 upregulation. The efficacy of EHMT2 inhibition was further confirmed in a 3D spheroid culture system, PDOs, and a xenograft model.</p><p><strong>Conclusions: </strong>Our findings suggest that EHMT2 is an attractive therapeutic target for GC treatment.</p>","PeriodicalId":12180,"journal":{"name":"Experimental Hematology & Oncology","volume":"13 1","pages":"86"},"PeriodicalIF":9.4,"publicationDate":"2024-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11334499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003964","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}