Journal of Hematology & Oncology最新文献

{"title":"Development and validation of a prognostic staging system for primary plasma cell leukemia","authors":"Mengru Tian, Gang An, Weijun Fu, Wenqiang Yan, Lu Li, Chunyan Sun, Zhenyu Li, Lijuan Chen, Aijun Liao, Guangxun Gao, Xiaoqi Qin, Mengyao Li, Chunrui Li, Hua Xue, Li Gao, Yi Wang, Aili He, Fan Zhou, Dongmei Guo, Yujun Dong, Zhihong Fang, Xiaoxia Chu, Jianqing Mi, Chengcheng Fu, Hui Zeng, Shuling Hou, Xiaotao Wang, Hua Wang, Yongqiang Wei, Xinyue Liang, Xingcheng Yi, Yue Sun, Lugui Qiu, Yun Dai, Fengyan Jin","doi":"10.1186/s13045-025-01723-0","DOIUrl":"https://doi.org/10.1186/s13045-025-01723-0","url":null,"abstract":"The existing risk models for multiple myeloma (MM) are suboptimal for the stratification of patients with primary plasma cell leukemia (pPCL), a rare and peculiar MM. In this study, we aimed to develop a staging system for pPCL defined as the presence of ≥ 5% circulating plasma cells (CPC) according to the new diagnostic criteria, utilizing one of the largest series of patients with pPCL. This multicenter retrospective study included 340 patients with pPCL (the training cohort) from 25 centers nationwide in China. The prognostic impact of baseline characteristics and cytogenetic abnormalities was evaluated. Univariate and multivariate analyses were conducted to identify variables predicting overall survival (OS) to develop a staging system. Its performance was then validated in an independent cohort (n = 80). Genome-wide DNA and RNA sequencing were performed to explore the molecular basis for inter-stage clinical heterogeneity. Del(17p), t(4;14), and t(14;16), but not 1q+, were verified as high-risk cytogenetic abnormalities (HRCAs) of pPCL. HRCA, elevated LDH, and thrombocytopenia had the highest impact on OS and were used to create a simple algorithm, stratifying patients with pPCL into stages I, II, and III, with median OS of 54.1, 24.0, and 5.4 months (II vs. I: HR, 1.986; 95% CI, 1.034–3.814; P = 0.0394; III vs. II: HR, 3.206; 95% CI, 1.757–5.852; P = 0.0001) in the training cohort and 62.1, 31.6, and 21.8 months (II vs. I: HR, 2.013; 95% CI, 0.954–4.251; P = 0.0664; III vs. II: HR, 2.694; 95% CI, 1.136–6.392; P = 0.0245) in the independent validation cohort. The accuracy (c-index 0.711) was higher than other models. Moreover, patients with different stages had highly diverse genomic and transcriptomic aberrations. We propose a pPCL-specific staging system based on LDH, thrombocytopenia, and cytogenetic abnormalities, which warrants further validation, particularly in a prospective setting.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"9 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629672","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":"Phase I first-in-human dose escalation study of the oral casein kinase 1α and cyclin dependent kinase 7/9 inhibitor BTX A51 in advanced MDS and AML","authors":"Brian J. Ball, Wenbin Xiao, Gautam Borthakur, Le Xuan Truong Nguyen, Melissa Valerio, Avanthika Venkatachalam, Guido Marcucci, Anthony S. Stein, Dung Luong Thai, David N. Cook, Kyle Chan, Sonali Persaud, Ross L. Levine, Omar Abdel-Wahab, Yinon Ben-Neriah, Eytan M. Stein","doi":"10.1186/s13045-025-01724-z","DOIUrl":"https://doi.org/10.1186/s13045-025-01724-z","url":null,"abstract":"BTX A51, a first-in-class oral small molecule inhibitor of casein kinase 1α (CK1α) and cyclin-dependent kinase (CDK) 7 and 9, induces apoptosis of leukemic cells by activating p53 and inhibiting expression of Mcl1. Here, we report on the results of the phase 1 clinical trial of BTX A51 in patients with relapsed or refractory AML and MDS. Adult patients with R/R AML and high-risk MDS were enrolled into eight potential doses ranging from 1 to 42 mg dosed orally three days/week for 21 or 28 days out of a 28-day cycle. The maximum tolerated dose, recommended phase 2 dose (RP2D), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of BTX A51 were investigated. Thirty-one patients were enrolled and received treatment with BTX A51. Median age was 75 (range 22- 84) and 55% were male. Most patients (97%) had received prior treatment with venetoclax and hypomethylating agents. The most common treatment-emergent adverse events of any grade were nausea (67%), emesis (63%), hypokalemia (53%), and diarrhea (40%). Two patients experienced hepatic toxicity as DLTs, which resolved upon holding treatment. No treatment-related deaths occurred. The recommended phase 2 dose was 21 mg dosed three days/week for 4 weeks of a 28-day cycle. BTX A51 increased the expression of p53 and reduced the expression of MCL1 and RNA polymerase II phosphorylation in pre- and post-treatment immunocytochemistry studies. Overall, 3 patients (10%) experienced complete remission with incomplete count recovery (CRi). All 3 responding patients had RUNX1 mutations and the CR/CRi rate for RUNX1-mutated patients receiving BTX A51 at efficacious doses (11 mg or higher) was 30%. Ex-vivo studies confirmed higher efficacy of BTX A51 on RUNX1-mutated myeloblasts and demonstrated synergy with azacitidine and venetoclax. Although the overall efficacy was modest, this study lays the groundwork for future studies with improved patient selection and combination approaches. NCT04872166.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"52 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144640353","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":"Treatment-related adverse events of antibody drug-conjugates in clinical trials","authors":"Harold Nathan Tan, Marta Ascanio Morcillo, Juanita Lopez, Anna Minchom, Adam Sharp, Alec Paschalis, Georgina Silva-Fortes, Bindu Raobaikady, Udai Banerji","doi":"10.1186/s13045-025-01720-3","DOIUrl":"https://doi.org/10.1186/s13045-025-01720-3","url":null,"abstract":"Antibody–drug conjugates (ADCs) aim to enhance the therapeutic index of cytotoxic agents but can cause unexpected toxicities. This study evaluated adverse events (AEs) from phase 1 trials at The Royal Marsden Drug Development Unit (DDU) over a decade and pivotal phase 2 and 3 trials leading to FDA registration, correlating AEs with ADC components such as target, antibody, linker, payload, and Drug-to-Antibody Ratio (DAR). We performed a retrospective cohort analysis of patients treated with ADCs in phase 1 trials (January 2014 to January 2024) compared to published phase 2–3 trials of FDA-approved ADCs. Univariate and multivariate logistic regression analyzed ADC components and treatment toxicities. One hundred thirty one phase 1 trial patients and 2666 phase 2–3 trial participants were included. High incidences of any-grade treatment-related AEs were observed (89% in phase 1, 93% in phase 2–3), with 58% experiencing grade 3 or higher toxicities in phase 1 and 46% in later phases. Major AEs included fatigue, hematologic toxicities, nausea/vomiting, ocular toxicities, and peripheral neuropathy. Antibody targets were linked to neuropathy, non-cleavable linkers to ocular, pulmonary, and hematologic toxicities, and tubulin-binding payloads to peripheral neuropathy. ADCs with DAR > 4 were associated with higher pulmonary and hematologic AEs. Despite their design to minimize toxicity, ADCs were linked to significant AEs. Specific ADC components may contribute to distinct toxicities, necessitating more robust trial data to inform future ADC design. ","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"20 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144547381","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":"Application of single-cell and spatial omics in deciphering cellular hallmarks of cancer drug response and resistance","authors":"Xiaoxia Cheng, Ting Peng, Tian Chu, Yiqun Yang, Jia Liu, Qinglei Gao, Canhui Cao, Juncheng Wei","doi":"10.1186/s13045-025-01722-1","DOIUrl":"https://doi.org/10.1186/s13045-025-01722-1","url":null,"abstract":"Drug resistance poses a significant challenge in cancer therapy, contributing to rapid recurrence, disease progression, and high patient mortality. Despite its critical impact, few reliable predictors for cancer drug response or failure have been established for clinical application. Tumor heterogeneity and the tumor microenvironment (TME) are pivotal factors influencing cancer drug efficacy and resistance. Tumor heterogeneity leads to variable therapeutic responses among patients, while dynamic interactions between cancer cells and the TME enhance tumor survival and proliferation, underscoring the urgent need to identify cellular hallmarks for predicting drug response and resistance. Single-cell and spatial omics technologies provide high-resolution insights into gene expression at the individual cell level, capturing intercellular heterogeneity and revealing the underlying pathologies, mechanisms, and cellular interactions. This review delves into the principles, methodologies, and workflows of single-cell and spatial omics in cancer drug research, highlighting key hallmarks involving tumor heterogeneity, TME reprogramming, cell–cell interactions, metabolic modulation, and signaling pathway regulation in drug treatment at single-cell and spatial levels. Furthermore, we synthesize predictive cellular biomarkers for cancer drug response and resistance across 25 cancer types, paving the way for advancements in cancer precision medicine.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"3 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533868","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":"CAR-T cells targeting CCR9 and CD1a for the treatment of T cell acute lymphoblastic leukemia","authors":"Néstor Tirado, Klaudyna Fidyt, María José Mansilla, Alba Garcia-Perez, Alba Martínez-Moreno, Meritxell Vinyoles, Juan Alcain, Marina García-Peydró, Heleia Roca-Ho, Narcis Fernandez-Fuentes, Mercedes Guerrero-Murillo, Aïda Falgàs, Talia Velasco-Hernandez, Clara Bueno, Patrizio Panelli, Vladimir Mulens-Arias, Apostol Apostolov, Pablo Engel, Europa Azucena González, Binje Vick, Irmela Jeremias, Aurélie Caye-Eude, André Baruchel, Hélène Cavé, Eulàlia Genescà, Jordi Ribera, Marina Díaz-Beyá, María Victoria Martínez-Sánchez, José Luis Fuster, Adela Escudero López, Jordi Minguillón, Antonio Pérez-Martínez, Manuel Ramírez-Orellana, Montserrat Torrebadell, Víctor M Díaz, María L Toribio, Diego Sánchez-Martínez, Pablo Menéndez","doi":"10.1186/s13045-025-01715-0","DOIUrl":"https://doi.org/10.1186/s13045-025-01715-0","url":null,"abstract":"T cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy characterized by high rates of induction failure and relapse, and effective targeted immunotherapies are lacking. Despite promising clinical progress with genome-edited CD7-directed CAR-T cells, which present significant logistical and regulatory issues, CAR-T cell therapy in T-ALL remains challenging due to the shared antigen expression between malignant and healthy T cells. This can result in CAR-T cell fratricide, T cell aplasia, and the potential for blast contamination during CAR-T cell manufacturing. Recently described CAR-T cells target non-pan-T antigens, absent on healthy T cells but expressed on specific T-ALL subsets. These antigens include CD1a (NCT05679895), which is expressed in cortical T-ALL, and CCR9. We show that CCR9 is expressed on >70% of T-ALL patients (132/180) and is maintained at relapse, with a safe expression profile in healthy hematopoietic and non-hematopoietic tissues. Further analyses showed that dual targeting of CCR9 and CD1a could benefit T-ALL patients with a greater blast coverage than single CAR-T cell treatments. We therefore developed, characterized, and preclinically validated a novel humanized CCR9-specific CAR with robust and specific antileukemic activity as a monotherapy in vitro and in vivo against cell lines, primary T-ALL samples, and patient-derived xenografts. Importantly, CCR9/CD1a dual-targeting CAR-T cells showed higher efficacy than single-targeting CAR-T cells, particularly in T-ALL cases with phenotypically heterogeneous leukemic populations. Dual CD1a/CCR9 CAR-T therapy may prevent T cell aplasia and obviate the need for allogeneic transplantation and regulatory-challenging genome engineering approaches in T-ALL.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"27 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144533865","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":"Therapeutic landscape of primary refractory and relapsed diffuse large B-cell lymphoma: Recent advances and emerging therapies","authors":"Allison M. Bock, Narendranath Epperla","doi":"10.1186/s13045-025-01702-5","DOIUrl":"https://doi.org/10.1186/s13045-025-01702-5","url":null,"abstract":"Diffuse large B-cell lymphoma (DLBCL) is an aggressive, yet curable malignancy, that has had practice changing treatment approvals in both the frontline and relapsed setting in the last 5 years. Advent of novel therapeutic options in the recent years has added greater complexity in treatment selection and optimal sequencing given multiple treatments with the same therapeutic target or immunotherapeutic mechanism of action. Key features impacting treatment selection include the timing of relapse, eligibility for curative options in the second line setting, including chimeric antigen receptor T-cell therapy (CAR-T) and autologous stem cell transplant (auto-SCT), as well as considerations of mechanism of action and side effect profile. This article provides a comprehensive review on recently approved therapies for relapsed or refractory DLBCL, emerging cellular and non-cellular therapies, and a summary of our approach to the management of these patients.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"71 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520889","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":"BRD4 acts as a transcriptional repressor of RhoB to inhibit terminal erythropoiesis","authors":"Yijin Chen, Dawei Huo, Ye Meng, Jie Zhang, Mengmeng Huang, Qian Luo, Yulin Xu, Haiqiong Zheng, Yingli Han, Xiangjun Zeng, Yanjuan Liu, Yunfei Liu, Rui Wen, Delin Kong, Ruxiu Tie, Shanshan Pei, Nan Liu, Pengxu Qian, He Huang, Meng Zhang","doi":"10.1186/s13045-025-01721-2","DOIUrl":"https://doi.org/10.1186/s13045-025-01721-2","url":null,"abstract":"Terminal erythropoiesis is a complex multistep process involving coordination of gene transcription and dramatic nuclear condensation, which leads to the expulsion of nuclei to generate reticulocytes. However, we lack a comprehensive understanding of the key transcriptional and epigenetic regulators involved. We used a high-throughput small molecule screen in primary CD34+-derived human erythroblasts to identify targets that promoted terminal erythropoiesis, and further confirmed the phenotype in different differentiation systems by inhibitors and shRNAs of different BRD4 isoforms. Then we performed RNA-seq, ATAC-seq, ChIP-qPCR, Co-IP, and reanalyzed previously-published transcriptional data and mass spectrometric data to clarify how BRD4 regulates terminal erythropoiesis. We identified that inhibitors of the bromodomain protein BRD4, an epigenetic reader and transcriptional activator together with CDK9, promoted terminal erythropoiesis from hematopoietic stem/progenitor cells and embryonic stem cells, and enhanced enucleation. Combined analysis of our RNA-seq, ATAC-seq, and previously-published transcriptional data of erythroblast differentiation at different stages confirmed that BRD4 inhibition accelerates erythroblast maturation. Unexpectedly, this BRD4 function was independent of its classical CDK9 interaction and transcriptional activation. Instead, RNA-seq, ATAC-seq, and Cut&Tag upon BRD4 inhibition revealed that BRD4 regulates erythropoiesis by inhibiting the small G protein RhoB and disrupts actin reorganization. ChIP-qPCR, Co-IP, and functional studies revealed that BRD4 acts as a transcriptional repressor by interacting with the histone methyltransferase EHMT1/2. We demonstrate a non-classical role for BRD4 as a transcriptional repressor of RhoB to regulate erythroid maturation, and classical CDK9 dependent role to regulate cell proliferation of erythroblasts. Besides, we clarify RhoB’s activity and function during terminal erythropoiesis. BRD4 inhibition might be a simple method to promote in vitro blood cell production, and a candidate therapeutic target for diseases leading to dyserythropoiesis such as myelodysplastic syndromes.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"633 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520890","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":"Deciphering cholangiocarcinoma heterogeneity and specific progenitor cell niche of extrahepatic cholangiocarcinoma at single-cell resolution.","authors":"Chunliang Liu,Xiang Wang,Erdong Liu,Yali Zong,Wenlong Yu,Youhai Jiang,Jianan Chen,Mingye Gu,Zhengyuan Meng,Jingfeng Li,Yang Liu,Yongjie Zhang,Jing Tang,Hongyang Wang,Jing Fu","doi":"10.1186/s13045-025-01716-z","DOIUrl":"https://doi.org/10.1186/s13045-025-01716-z","url":null,"abstract":"BACKGROUNDCholangiocarcinoma (CCA) is a highly heterogeneous malignancy, primarily comprising intrahepatic (iCCA) and extrahepatic (eCCA) subtypes. Reconciling the variability between iCCAs and eCCAs in clinical trials remains a challenge, largely due to the inadequate understanding of their shared and subtype-specific cellular heterogeneity. We aim to address this issue using single-cell and spatially resolved transcriptomic approaches.METHODSWe performed comprehensive single-cell RNA sequencing (scRNA-seq) by profiling 109,071 single cells from 28 samples, including chronic biliary inflammatory conditions (n = 7) and CCAs from different anatomical sites (n = 21). Findings were validated using external multi-omics datasets, tissue microarray cohort, spatial RNA in situ sequencing, CCA patient-derived organoids (PDOs), and mouse models.RESULTSiCCAs and eCCAs exhibited distinct tumor ecosystems, with notable differences in cellular composition, diversity, and abundance across various cell types. Non-malignant epithelial cells displayed divergent precancer hallmarks from different biliary sites, with inflammatory extrahepatic bile ducts exhibiting early hijacking of the gastrointestinal metaplastic process. We identified seven meta-programs within cancer cells, mapped into four major subtypes. This subtyping was validated using external CCA cohorts and PDO models, distinguishing patients based on clinical outcomes and drug vulnerabilities. Specifically, iCCAs were associated with a senescent program, while eCCAs were enriched in an IFN-responsive program linked to adverse clinical outcomes and increased drug resistance. We identified a basal-like LY6D+ cancer cell subpopulation specific to eCCAs, which displayed significant stemness, drug resistance, and IFN-responsive features. This subpopulation was closely associated with an interferon-stimulated gene 15 (ISG15)-enriched mesenchymal and immune microenvironment. Functional assays demonstrated that ISG15 stimulation significantly boosted stemness, basal-like features, and drug resistance in eCCA cells, highlighting its pivotal role in sustaining the LY6D+ progenitor niches.CONCLUSIONWe present a comprehensive single-cell landscape of CCAs, uncovering the molecular heterogeneity between iCCA and eCCA subtypes. Transcriptomic subtyping of CCA cancer cells offers implications for clinical stratification and functional precision oncology. We identify basal-like epithelial progenitors and characterize their associated ISG15-enriched microenvironment in eCCAs. These findings hold significant promise for the development of novel prognostic biomarkers, therapeutic targets, and treatment strategies for CCAs.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"8 1","pages":"66"},"PeriodicalIF":28.5,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144370199","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":"Extracellular matrix dynamics in tumor immunoregulation: from tumor microenvironment to immunotherapy","authors":"Qin Hu, Yifei Zhu, Jie Mei, Ying Liu, Guoren Zhou","doi":"10.1186/s13045-025-01717-y","DOIUrl":"https://doi.org/10.1186/s13045-025-01717-y","url":null,"abstract":"The extracellular matrix (ECM), closely linked to the dynamic changes in the tumor microenvironment (TME), plays a critical role in modulating tumor immunity. The dual role of the ECM in tumor progression, encompassing both promotion and inhibition, is attributed to its components influencing immune cell activation, migration, and infiltration. This mechanism is intricately connected with the efficacy of immunotherapies. Currently, there is limited understanding of how ECM remodeling spatially and temporally coordinates with immune checkpoint inhibitors (ICIs) or adoptive cell therapies. Furthermore, strategies to selectively target pathological ECM components while preserving their homeostatic functions urgently require systematic investigation. In this review, we summarize current findings on the interplay between ECM and tumor immune regulation, with a particular focus on how key ECM components contribute to immune modulation. Furthermore, we discuss emerging strategies targeting ECM-related mechanisms to enhance the efficacy of immunotherapies, including approaches that remodel the ECM to improve immune infiltration and strategies that synergize with existing immunotherapies. By integrating these insights, we provide a perspective on leveraging ECM-targeted interventions to overcome immune evasion and optimize cancer immunotherapy outcomes.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"30 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319753","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":"Menin inhibitors from monotherapies to combination therapies: clinical trial updates from 2024 ASH annual meeting","authors":"Gejia Cao, Haixiao Zhang, Shu Sun, Hong-Hu Zhu","doi":"10.1186/s13045-025-01718-x","DOIUrl":"https://doi.org/10.1186/s13045-025-01718-x","url":null,"abstract":"Menin inhibitors, which target the KMT2A-menin protein-protein interaction to inhibit blasts proliferation and induce differentiation, have demonstrated potential effects on acute leukemia subtypes characterized by overexpression of HOXA gene cluster and MEIS1 (including KMT2A rearrangements, NPM1 mutations, NUP98 rearrangements and other genetic alterations). Following the promising outcomes of the two pioneering menin inhibitors, revumenib and ziftomenib, other menin inhibitors, including bleximenib, enzomenib, BN-104 and HMPL-506 are currently under investigation in clinical trials. Several trials presented their initial outcomes at the 2024 ASH Annual Meeting. This review highlights the key outcomes of these pivotal clinical trials.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"7 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144304719","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}