Journal of Hematology & Oncology最新文献

{"title":"BCMA-CD19 armored compound CAR T cells in systemic lupus erythematosus: extended follow-up of a phase 1 clinical trial.","authors":"Ming Hong,Mingxia Wang,Ronghao Zeng,Ling Ding,Shanzhi He,Ting Lan,Vincent M DeStefano,Masayuki Wada,Kevin Pinz,Jennifer E Chow,Byeong Hyeok Choi,Nabil Hagag,Min Wang,Yu Ma,Jing Luo,Yingwen Liang,Shihao Ding,Ziji Lu,Wenli Zhang,Yupo Ma,Weijia Wang","doi":"10.1186/s13045-026-01779-6","DOIUrl":"https://doi.org/10.1186/s13045-026-01779-6","url":null,"abstract":"CD19 CAR T-cells have shown promise in treating systemic lupus erythematosus (SLE), however, relapses demonstrate persistently elevated autoantibodies characteristic of CD19-negative long-lived plasma cells (LLPCs). Alternatively, ICG318, a dual-targeting BCMA-CD19 armored CAR T-cell therapy, targets both B cells and plasma cells/LLPCs driving SLE which may improve outcomes. Herein, we present 12 patients with refractory SLE, including 10 with lupus nephritis (LN), who received ICG318 CAR T-cells resulting in 10 of 12 achieving stringent complete remission (sCR) defined by medication-free DORIS CR and complete renal response (CRR). Eleven of 12 achieved drug-free, serological CR. Nine patients underwent repeat renal biopsy demonstrating evidence of remarkable histological improvement with clearance of immune-complex deposits and resolution of chronic glomerular injury. The safety profile was favorable, with no high-grade cytokine release syndrome or neurotoxicity. Notably, successful spontaneous pregnancies and births of healthy full-term infants occurred post-treatment, warranting future study of fertility outcomes. sCR approaching 6 years raises the possibility of a long-term durable response to CAR T-cell therapy in humoral autoimmune disease.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"261 1","pages":"13"},"PeriodicalIF":28.5,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146073080","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":"CBX3 confers ferroptosis resistance during blood-borne metastasis.","authors":"Chun Wu,Xuefei Liu,Boxi Zhao,Mao Zhao,Binyu Zhang,Guanyin Huang,Yixin Cheng,Shuqian Zheng,Jianyang Hu,Ling Guo,Weinan Guo,Jun Tan,Xin Hong","doi":"10.1186/s13045-025-01777-0","DOIUrl":"https://doi.org/10.1186/s13045-025-01777-0","url":null,"abstract":"The survival mechanisms of circulating tumor cells (CTCs) remain poorly understood while these rare cell populations transit through the blood stream and colonize distant organs including the brain. Using single-cell RNA-seq of microfluidically-enriched CTCs and patient-matched brain metastatic tumor cells of lung adenocarcinoma (LUAD), we revealed CTC-selective upregulation of core gene signatures associated with ferroptosis. The malignancy of CTCs was confirmed through comparative genomic instability and copy number variation (CNV) analyses of paired CTCs and metastatic tumor cells using both transcriptomic and whole-exome sequencing. Among the transcription factors elevated in CTCs, Chromobox 3 (CBX3) was the top hit, which was tightly correlated with GPX4 expression. Functionally, CBX3 co-operated with EP300 to protect CTCs from ferroptosis by upregulating GPX4 expression. Genetic depletion of CBX3 triggered ferroptosis and substantially reduced tumor cell survival and invasiveness in two independent cancer cell models. Conversely, CBX3 overexpression was sufficient to promote tumor growth, migration, and invasion in vitro, and metastatic progression in vivo. Clinically, CBX3 expression was significantly correlated with TNM stage and was predictive of both progression-free interval and overall survival in LUAD. In a prospective cohort of LUAD and melanoma patients, CTCs co-expressing CBX3 and GPX4 were selectively elevated in the blood samples of metastatic cases compared to the non-metastatic group, highlighting the clinical association between ferroptosis-resistant CTCs and metastatic progression.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"221 1","pages":"9"},"PeriodicalIF":28.5,"publicationDate":"2026-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986504","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":"Patterns, risk factors and management of CD19-directed chimeric antigen receptor T-cell therapy failure in CNS lymphoma.","authors":"Leon D Kaulen,Philipp Karschnia,Sofia Doubrovinskaia,Jeremy S Abramson,Jacob D Soumerai,Maria Martinez-Lage,J Erika Haydu,Ganesh M Shankar,Chirayu Patel,Bryan D Choi,Jeffrey A Barnes,Areej El-Jawahri,Ephraim P Hochberg,P Connor Johnson,Wolfgang Wick,Marcela V Maus,Yi-Bin Chen,Matthew J Frigault,Jorg Dietrich","doi":"10.1186/s13045-025-01761-8","DOIUrl":"https://doi.org/10.1186/s13045-025-01761-8","url":null,"abstract":"BACKGROUNDCD19-directed chimeric antigen receptor T-cell therapy (CD19-CAR) has yielded encouraging efficacy in CNS lymphomas (CNSL), but most patients ultimately experience progressive disease (PD). Risk factors, progression patterns as well as optimal salvage therapies remain unclear.METHODSClinical and radiological characteristics of CD19-CAR failure were therefore retrospectively defined in CNSL treated at Massachusetts General Hospital from 2018 to 2024. PD patterns were defined as local or distant. CNS-progression-free survival from CD19-CAR infusion (CNS-PFS1) and first subsequent progression (CNS-PFS2) were analyzed.RESULTSCD19-CAR achieved a 60% overall response rate (45% complete (CR), 15% partial response) in 60 recurrent CNSL. Median CNS-PFS1 was 4 months with radiographic PD in 36 patients (local 23.3%; local and distant 16.7%; distant 20%). PD patterns were associated with prior CD19-CAR response: Distant relapse typically occurred after CR whereas local PD followed CD19-CAR refractory disease. Peripherally contrast enhancing CNSL (pCE) at CD19-CAR infusion correlated with refractory disease. Leptomeningeal involvement (LMD) was associated with recurrence after CR. On multivariable Cox regression, pCE (Hazard ratio [HR]: 2.75; 95%-Confidence interval [CI]: 1.08-6.68, p = 0.03) and LMD (HR: 2.72; CI: 1.20-6.25, p = 0.02) were independently associated with shorter CNS-PFS1. At progression, peripheral CD19+-B-cell aplasia suggested CD19-CAR persistence in 93% of patients. Median CNS-PFS2 after CD19-CAR failure was one month. Salvage immune checkpoint inhibition, and lenalidomide with rituximab/tafasitamab yielded prolonged responses.CONCLUSIONSThis study identifies novel radiological risk factors for CD19-CAR failure in CNSL, namely pCE and LMD. Outcome in this setting is unfavorable and encouraging salvage treatments warrant prospective evaluation.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"21 1","pages":"2"},"PeriodicalIF":28.5,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145961414","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":"Molecularly targeted therapy and immunotherapy in leukemias.","authors":"Elie Cousin,Agathe Picard,Maria Oundjian,Nina Tardif,Anaïs Quemener,Anne-Gaëlle Rio,Marie-Dominique Galibert,Virginie Gandemer,Frédéric Mazurier","doi":"10.1186/s13045-025-01775-2","DOIUrl":"https://doi.org/10.1186/s13045-025-01775-2","url":null,"abstract":"The advent of next-generation high-throughput sequencing and precision medicine has allowed the identification of recurrent genetic events of vital interest for leukemic cells and for the management of patients with leukemia, since it has a direct impact on prognosis and therapeutic stratification. The precise cytogenetic characterization of these diseases has rapidly enabled the development of innovative therapeutic strategies to improve outcomes and limit toxicities. New targeted therapies, including small molecule inhibitors, monoclonal antibodies, bispecific T cell engagers, antibody-drug conjugates, recombinant immunotoxins, and chimeric antigen receptor T cells (CAR-T cells) represent a broad therapeutic arsenal now available in everyday practice. The growing number of treatments means that many possibilities of drugs and combinations can be used to offer new lines of therapy in cases of refractory disease or relapse, but also in frontline treatment. This review provides a broad overview of pathogenic mechanisms and therapies (including targeted therapies, immunotherapy and RNA-based therapy) and gathers the main research progress in the field of leukemia.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"24 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949740","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":"Clinical validation of UroCAD test for upper tract urothelial carcinoma detection: results from a prospective multi-center study.","authors":"Guoliang Yang, Shuxiong Zeng, Wei He, Lianhua Zhang, Chuanliang Xu, Jiahua Pan, Wei Xue","doi":"10.1186/s13045-025-01772-5","DOIUrl":"10.1186/s13045-025-01772-5","url":null,"abstract":"<p><strong>Background: </strong>Upper tract urothelial carcinoma (UTUC) poses diagnostic challenges due to its anatomical complexity and limited accessibility.</p><p><strong>Methods: </strong>This prospective multicenter study (NCT05043662) evaluated the diagnostic performance of UroCAD, a novel non-invasive assay based on chromosomal copy number variation (CNV) analysis, in 244 patients with suspected UTUC or benign upper urinary tract conditions.</p><p><strong>Results: </strong>Urine samples were analyzed for arm-level chromosomal aberrations (|Z-score|≥ 3.21), with histopathology as the reference standard. UroCAD demonstrated excellent diagnostic accuracy: sensitivity 91.0%, specificity 97.0%, and overall accuracy 93.4%. Performance was consistent across tumor locations (renal pelvis: 96.8%, ureter: 86.4%) and grades (high-grade: 93.5%, low-grade: 76.2%). Compared to urine cytology, UroCAD showed significantly higher sensitivity (91.2% vs. 52.9%, P < 0.001). CNV profiling revealed grade-associated patterns, with high-grade tumors frequently exhibiting amplifications on 1q and 8q. The extent (MaxZ) and number (CountZ) of chromosomal alterations correlated positively with tumor grade, supporting UroCAD's potential utility in molecular grading.</p><p><strong>Conclusions and clinical implications: </strong>The UroCAD test demonstrates robust diagnostic performance for UTUC detection with high specificity and high sensitivity. The consistent performance across various clinical scenarios and the identification of specific chromosomal alteration patterns support its potential as a valuable clinical tool for both initial diagnosis and treatment monitoring. These findings warrant larger-scale validation studies to confirm its utility in routine clinical practice.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"19 1","pages":"8"},"PeriodicalIF":40.4,"publicationDate":"2026-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12784582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933709","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":"Multicenter real-life evaluation of the Post-CAR prognostic index for patients with large B-cell lymphoma after CAR-T failure.","authors":"Mirko Farina, Elena Maiolo, Chiara Ghiggi, Piera Angelillo, Mattia Novo, Francesca Maria Quaglia, Luana Schiattone, Marta Lisa Battista, Lara Mannelli, Valeria Tomarchio, Elisa Lucchini, Luca Pagliaro, Greta Scapinello, Miriam Marangon, Sabrina Pelliccia, Roberta Sciarra, Domenico Russo, Francesco Zaja","doi":"10.1186/s13045-025-01771-6","DOIUrl":"10.1186/s13045-025-01771-6","url":null,"abstract":"<p><p>Most patients with large B-cell lymphoma (LBCL) progressing after CAR-T therapy experience poor survival and lack standardized treatment strategies. Prognostic tools are needed to guide decision-making at relapse. The Post-CAR Prognostic Index (PC-PI), recently proposed by Iacoboni et al., combines five routine clinical variables to stratify outcomes after CAR-T failure: ECOG (> 0), hemoglobin (< 10 g/dL), LDH (≥ 2xULN), number of extranodal sites (> 1) and time from CAR-T to progression (< 4 months). We evaluated the PC-PI in a retrospective multicenter study including 125 LBCL patients relapsing or refractory after axicabtagene-ciloleucel or tisagenlecleucel, treated between 2019 and 2023 across 16 Italian centers belonging to the Fondazione Italiana Linfomi network. Median overall survival (OS) was 4.9 months, with 6- and 12-month OS rates of 44.9% and 28.5%, respectively. The PC-PI discriminated prognosis effectively: high-risk patients had a median OS of 1.8 months, intermediate-high 2.2, intermediate-low 8.7, while in the low-risk group median OS was not reached (p<0.0001). Results remained consistent after excluding patients receiving only palliative care. Post-progression therapy markedly influenced survival: patients receiving active treatment achieved a median OS of 7.3 months versus 0.7 without further therapy (p<0.0001). Bispecific antibodies conferred the best outcomes (HR 0.44, p=0.02), with 6- and 12-month OS rates of 90% and 55%. Our findings confirm the prognostic value of the PC-PI and support its use in clinical practice as a tool for risk-adapted management of LBCL after CAR-T failure.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"19 1","pages":"4"},"PeriodicalIF":40.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12784594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933756","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":"A subcellular spatial atlas illuminates the microenvironmental remodeling of perineural invasion in distal cholangiocarcinoma.","authors":"Fansen Ji, Hao Chen, Huan Li, Jiawei Zhang, Sijia Li, Pengfei Wang, Hao Liu, Cui Ge, Bingjun Tang, Hongfang Yin, Xuedong Wang, Jiahong Dong","doi":"10.1186/s13045-025-01773-4","DOIUrl":"10.1186/s13045-025-01773-4","url":null,"abstract":"<p><p>Distal cholangiocarcinoma (dCCA) arises from the distal bile duct and is anatomically embedded within the pancreatic head, adjacent to abundant autonomic nerve plexuses. This unique location renders dCCA particularly prone to perineural invasion (PNI), a pathological hallmark that contributes to its dismal prognosis. However, the spatial architecture and molecular drivers that orchestrate PNI remain poorly defined. Here, we applied Xenium subcellular resolution spatial transcriptomics platform to profile resected tumor tissues from dCCA patients stratified by PNI status pathologically. A spatially resolved atlas comprising a total of 20 cell types was generated, uncovering enrichment of Schwann cells, type 2 conventional dendritic cells (cDC2), M2-like macrophages, cancer associated fibroblasts (CAFs) and B/plasma cells in PNI-high tumors, along with depletion of exhausted CD8⁺ T cells. Heterogeneous malignant cells in PNI-high tumors demonstrated activation of extracellular matrix remodeling and axonogenesis pathways, in line with the initial pathological classification. Spatial mapping further revealed distinct PNI-associated niches, notably matrix-producing CAFs (mCAFs)-macrophage clusters exhibiting coordinated enrichment of inflammatory and fibrotic programs. We further identified the LAMB3-DAG1 axis as a potential mediator of dCCA cells-Schwann cell interaction, while the preferential proximity of arteries to Schwann cells suggested additional microenvironmental support for nerve invasion. Collectively, our study provides a comprehensive subcellular atlas of PNI in dCCA, uncovering coordinated epithelial, stromal, and immune remodeling that drives perineural invasion. The identified biomarkers not only hold promise for patient stratification but may also guide intraoperative navigation and surgical margin determination, offering new avenues for precision therapy.</p>","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"19 1","pages":"6"},"PeriodicalIF":47.8,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12784525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145933670","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":"Multiple myeloma risk linked to DNA damage response genes.","authors":"Michael Conry,Irina Ostrovnaya,Yelena Kemel,Saloni Sinha,Linda B Baughn,Brian Avery,Kylee Maclachlan,Victoria Groner,Lauren Banaszak,Aaron Norman,Nicholas J Boddicker,Alyssa Clay-Gilmour,Shaji Kumar,Ellen Kim,Sita Dandiker,Mitul Waghmare,Susan Slager,Douglas W Sborov,Judy Garber,Elizabeth E Brown,Michelle Hildebrandt,Parameshwaran Hari,Nicola Camp,Celine Vachon,Saad Usmani,Kenneth Offit,Vijai Joseph","doi":"10.1186/s13045-025-01776-1","DOIUrl":"https://doi.org/10.1186/s13045-025-01776-1","url":null,"abstract":"BACKGROUNDDNA damage response genes (DDRG), implicated in several cancers as both predisposing risk factors as well as biomarkers for aggressiveness, have not been fully explored in multiple myeloma (MM).METHODSHerein, we analyzed disease associations of pathogenic variations in nine putative candidate genes using 3 446 MM cases and 323 233 cancer-free controls.RESULTSIncreased MM risk was found to be associated with inherited rare pathogenic mutations in TP53, ATM, CHEK2, KDM1A, and ARID1A, with an enrichment of these variants among individuals with early onset or family history of MM. Individuals with TP53 or ATM germline mutations are also likely to have worse overall survival.CONCLUSIONSOur results suggest expansion of the phenotypic spectrum of some of these DDRG to include MM. The identification of these germline predisposition genes opens the avenue for targeted screening of higher risk individuals especially those with young-onset or a family history of plasma cell gammopathies.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"32 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145907673","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":"CD47 blockade-driven necroptosis complements BCL-2 inhibition-driven apoptosis in lymphoid malignancies.","authors":"Stephen J F Chong,Rebecca Valentin,Jing Wang,Fen Zhu,Prafulla C Gokhale,Benjamin K Eschle,Filip Garbicz,Kartini Iskandar,Tomasz Sewastianik,Brienne C Y Toh,Johany Penailillo,Marisa O Peluso,Jeremy Zhang,Liam Hackett,Mary C Collins,Timothy Z Lehmberg,Ammar Adam,Li Zhang,Caroline M Armet,Matthew Rausch,Benjamin H Lee,Pamela M Holland,Vito J Palombella,Alison M Paterson,Li Ren Kong,Elisa Ten Hacken,Jennifer L Guerriero,Charles Herbaux,Catherine J Wu,Wee Joo Chng,Shazib Pervaiz,Carsten U Niemann,Ruben D Carrasco,Matthew S Davids","doi":"10.1186/s13045-025-01774-3","DOIUrl":"https://doi.org/10.1186/s13045-025-01774-3","url":null,"abstract":"","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"19 1","pages":""},"PeriodicalIF":28.5,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145893955","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":"Aberrant KIF26B expression promotes bladder cancer progression through driving NSUN2 nuclear localization.","authors":"Jia-Ming Wang,Hai-Yun Xie,Feng-Hao Zhang,Xuan Shu,Jin-Dan Luo,Li-Ping Xie,Jiang-Feng Li","doi":"10.1186/s13045-025-01749-4","DOIUrl":"https://doi.org/10.1186/s13045-025-01749-4","url":null,"abstract":"Abnormal expression of kinesins has been observed in several types of cancer. The present study provided the first evidence that KIF26B could induce RNA m5C modification in bladder cancer (BCa). Detailly, KIF26B interacted with NSUN2 and recruited ubiquitinase STUB1 to promote K63-linked ubiquitination of NSUN2 at K511 site. K63-linked ubiquitination enabled NSUN2 to bind to KPNA1 and translocate into nucleus where it drove RNA m5C modification. Furthermore, KIF26B induced liquid-liquid phase separation (LLPS) of YBX1 and upregulated IL-6 expression through NSUN2/m5C/YBX1 axis. Secreted IL-6 then activated STAT3 signaling to promote transcription of kif26b through direct binding between STAT3 and kif26b promoter. IL-6 also recruited DLAT to acetylate NSUN2 at K229 site and increased association affinity between NSUN2 and KIF26B. Together, these established a KIF26B/NSUN2/m5C/IL-6 positive feedback loop, suggesting that targeting KIF26B may be a promising therapeutic strategy for BCa.","PeriodicalId":16023,"journal":{"name":"Journal of Hematology & Oncology","volume":"21 1","pages":"110"},"PeriodicalIF":28.5,"publicationDate":"2025-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145801322","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}