Blood advances最新文献

{"title":"Restarting Teclistamab and Talquetamab after Prolonged Dose Delay May Not Require Re-Step-up Dosing.","authors":"Carlyn R Tan, Alice X Wang, David Nemirovsky, Andriy Derkach, Tala Shekarkhand, Issam S Hamadeh, Kylee H Maclachlan, Malin L Hultcrantz, Hani Hassoun, Sham Mailankody, Alexander M Lesokhin, Urvi A Shah, Sridevi Rajeeve, Hamza Hashmi, Dhwani Patel, Ross S Firestone, Eric Matthew Jurgens, Kevin C Miller, Gunjan L Shah, Michael Scordo, Heather J Landau, Sergio A Giralt, Neha Korde, Saad Z Usmani","doi":"10.1182/bloodadvances.2024015344","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015344","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572167","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 Outcomes in Elderly Patients Treated Outside Clinical Studies: Highlighting the Octogenarian Experience.","authors":"Dor Shpitzer, Yael C Cohen, Tamir Shragai, Ori Grossberger, Dana Amsterdam, Anat Reiner-Benaim, Irit Avivi","doi":"10.1182/bloodadvances.2025015968","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025015968","url":null,"abstract":"<p><p>With an aging population, multiple myeloma (MM) increasingly affects octogenarians (Octo, ≥80 years), but data on their management and outcomes, particularly if treated outside clinical trials, remain limited. This retrospective study analyzed 652 patients aged ≥70 years, diagnosed with active MM between 2014 and 2023, identified in the Maccabi Healthcare Services medical records. Patient characteristics, treatment, time to next treatment (TTNT), overall survival (OS), and factors influencing outcomes, were compared between Octo and elderly (EL) patients aged 70-<80 years. The results show that Octo patients (median age 83 years) had more comorbidities (mean 3 vs. 2) and higher Charlson comorbidity scores than EL (≥6, 53% vs. 23%, p<0.001), leading to lower rates of anti-MM therapy administration (83% vs. 96%, p<0.001) and reduced triplet/quadruplet (n=87/5) use (38.8% vs. 55%, p=0.02). Over a median follow-up of 25 months (0.1-124), Octo patients had significantly shorter median OS; 25.9 vs. 71.3 months, (p<0.001), and 33 vs. 76.9 months among treated patients only (p<0.001). TTNT was similar (17.8 vs. 22.1 months, p=0.43). Multivariate analysis showed triplet/quadruplet to be associated with improved TTNT (HR 0.61, p<0.001) and OS (HR 0.63, p<0.001) compared to doublets, while higher Charlson scores and age ≥80 years predicted worse OS (HR 1.5, p=0.003, HR 2.27, p<0.001). Daratumumab-based therapies enhanced TTNT in both age groups (HR 0.54, p=0.017). In conclusion, higher comorbidities in Octo patients adversely affected their management and survival. However, daratumumab positively influenced outcomes, underscoring the need for tailored approaches to optimize treatment in older MM patients.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572164","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":"Neutrophil recruitment depends on platelet-derived leukotriene B4.","authors":"Christian Hackenbroch, Tugce Cimen, Carina Gross, Stefanie Rubenzucker, Philipp Burkard, Niklas Groß, Robert Ahrends, Tamara Girbl, David Stegner","doi":"10.1182/bloodadvances.2024014947","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024014947","url":null,"abstract":"","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572166","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":"DNMT3A regulates murine megakaryocyte-biased hematopoietic stem cell fate decisions.","authors":"Sarah M Waldvogel, Virginia Camacho, Dandan Fan, Anna Guzman, Alejandra Garcia-Martell, Elmira Khabusheva, Jacey Rodriguez Pridgen, Josephine De La Fuente, Rachel E Rau, Ashlyn Laidman, Maria N Barrachina, Estelle Carminita, Justin Andrew Courson, Michael Williamson, Joanne Ino Hsu, Chun-Wei Chen, Jaime Reyes, Subhashree Pradhan, Rolando Rumbaut, Alan Burns, Benjamin Deneen, Jianzhong Su, Kellie R Machlus, Margaret A Goodell","doi":"10.1182/bloodadvances.2024015061","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015061","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) are defined by their capacity to regenerate all main components of the peripheral blood, but individual HSCs exhibit a range of preferences for generating downstream cell types. Their propensities are thought to be epigenetically encoded, but few differential regulatory mechanisms have been identified. In this work, we explored the role of the DNA methyltransferase 3A (DNMT3A) in the megakaryocyte-biased HSC population, which is thought to reside at the top of the hematopoietic hierarchy. We demonstrate that heterozygous loss of DNMT3A (Dnmt3a+/-) in these megakaryocyte-biased HSCs has consequences distinct from the rest of the HSC pool. These megakaryocyte-biased HSCs become delayed in their lymphoid-repopulating ability but can ultimately regenerate all lineages. We further demonstrate that Dnmt3a+/- mice have increased numbers of megakaryocytes in the bone marrow. Analysis of DNA methylation differences between WT and Dnmt3a+/- HSC subsets, megakaryocyte-erythroid progenitors (MEP), and megakaryocytes revealed that DNA methylation is eroded in the mutants in a cell type-specific fashion. While transcriptional differences between the WT and Dnmt3a+/- megakaryocyte-biased HSCs are subtle, the pattern of DNA methylation loss in this HSC subset is almost completely different from that in non-megakaryocyte-biased HSCs. Together, our findings establish the role of epigenetic regulation in the fate of megakaryocyte-biased HSCs and their downstream progeny and suggest that the outcomes of DNMT3A loss might vary depending on the identity of the HSC that acquires the mutation.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572165","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":"Safety Run-In and Part 1 of GIMEMA AML1718: Venetoclax Combined with FLAI as Induction Treatment in Non-Low-Risk AML.","authors":"Giovanni Marconi, Alfonso Piciocchi, Ernesta Audisio, Cristina Papayannidis, Marco Cerrano, Clara Minotti, Francesca Paoloni, Fabio Guolo, Monica Bocchia, Michela Rondoni, Albana Lico, Matteo Giovanni Carrabba, Matteo Giovanni Della Porta, Marco Frigeni, Luisa Giaccone, Germana Beltrami, Chiara Cattaneo, Maria Chiara Di Chio, Bianca Serio, Enrico Crea, Roberto Freilone, Saveria Capria, Antonio Curti, Paola Minetto, Edoardo la Sala, Jacopo Nanni, Beatrice Anna Zannetti, Giorgia Simonetti, Maria Teresa Bochicchio, Giuseppe Saglio, Roberto Massimo Lemoli, Adriano Venditti, Marco Vignetti, Paola Fazi, Giovanni Martinelli","doi":"10.1182/bloodadvances.2024014901","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024014901","url":null,"abstract":"<p><p>The standard induction treatment for acute myeloid leukemia (AML) has limited efficacy for patients with non-low-risk AML. We conducted a multicenter study phase 1b/2, GIMEMA AML1718, to investigate the safety and efficacy of venetoclax (VEN) combined with fludarabine, cytarabine, and idarubicin (V-FLAI) as an induction therapy for non-low-risk AML patients younger than 65 years and at intermediate or high ELN risk. After a safety run-in, patients were randomly allocated to VEN 400 mg or VEN 600 mg cohorts. The primary objectives were safety and composite complete remission (bone marrow blasts <5% with any recovery). We report a predefined interim analysis after 57 patients. Median exposure to VEN during induction was 22 days. Effectiveness and safety were similar between VEN 400 mg and VEN 600 mg cohorts. 60-days mortality was 5.8%. Prolonged aplasia was observed in patients receiving high doses of cytarabine during consolidation. cCR, was achieved in 84% of patients. With a median follow-up of 20.6 months, 1-year overall survival was 71%, 1-year disease free survival was 66.2%, 1-year cumulative incidence of relapse was 24%. V-FLAI is an effective induction therapy for young and fit patients. Fifty-five more patients will be enrolled in part 2; they will receive VEN 400 mg-FLAI as predefined and will be centrally evaluated for measurable residual disease. NCT03455504.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572168","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":"Transplant Outcomes Using Older Matched Sibling Donors Compared to Young Alternative Donors: A CIBMTR Analysis.","authors":"Karthik Nath, Mei-Jie Zhang, Matthew Bye, Muhammad Bilal Abid, Cara Benjamin, Brian C Betts, Neel S Bhatt, Esteban Arrieta-Bolaños, Yung-Tsi Bolon, Shahinaz M Gadalla, Michael R Grunwald, Maxwell M Krem, Stephanie J Lee, Steven G E Marsh, Rodrigo Martino, Parinda A Mehta, Filippo Milano, Timothy Prestidge, Jennifer N Saultz, Bronwen E Shaw, Stephen R Spellman, Hannah K Choe, Brian C Shaffer","doi":"10.1182/bloodadvances.2024014858","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024014858","url":null,"abstract":"<p><p>Whether younger donors should be prioritized over HLA-matching for allogeneic hematopoietic cell transplantation (allo-HCT) when using post-transplant cyclophosphamide (PTCy)-based graft versus host disease (GvHD) prophylaxis is unclear. To address this, we compared outcomes of allo-HCT recipients aged ≥50-years using PTCy-based GvHD prophylaxis from an older (≥50-years) matched sibling donor (MSD) to those of younger alternative donors ≤35-years: HLA-matched unrelated donors (MUD), HLA-mismatched unrelated donors (MMUD), and haploidentical (haplo)-related donors reported to the Center for International Blood & Marrow Transplant Research between 2014-2021. Young MUD and older MSD receiving calcineurin inhibitor (CNI)-based allo-HCT that met study criteria were concurrently examined. The primary endpoint was overall survival (OS). Among 14,662 HCT recipients, 3,746 received PTCy- and 10,916 CNI-based GvHD prophylaxis. The median follow-up was 47 months. In patients treated with PTCy, the adjusted 5-year OS was not significantly different at 44% for MSD compared with 52% for MUD (multivariable hazard ratio [HR]: 1.20, 95%CI: 1.03-1.41, p=0.09), 45% for haplo (HR: 1.02, 0.88-1.18, p=1.00) and 46% for MMUD (HR: 1.00, 0.83-1.21, p=1.00). Compared to MSDs, receipt of younger MUD associated with improved disease-free survival (DFS) both with PTCy (HR: 1.21, 1.05-1.40, p=0.048) and CNI (HR 1.09, 1.04-1.15, p<0.01) based prophylaxis. Haplo-donor recipients associated with similar OS to MSD, but worse OS compared to MUD recipients with PTCy (HR: 1.18, 1.05-1.33, p=0.04). These data suggest that older MSDs result in similar OS compared to younger alternative donors in older-aged recipients. Younger MUDs may be preferred for older patients due to improved DFS when available.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572170","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":"Targeting the RBM39-MEK5 axis synergizes with bortezomib to inhibit the malignant growth of multiple myeloma.","authors":"Jia Liu, Zilu Zhang, Wenbin Xu, Mingyuan Jia, Xinyi Zeng, Chengyu Wu, Ze Fu, Xiaoguang Xu, Chenjing Ye, Chao Wu, Hanzhang Xu, Hu Lei, Ying-Li Wu, Yan Hua","doi":"10.1182/bloodadvances.2025015815","DOIUrl":"https://doi.org/10.1182/bloodadvances.2025015815","url":null,"abstract":"<p><p>Aberrant alternative splicing is one of the hallmarks of cancer and is potentially based on upregulated expression of splicing factors in some types of cancer. Our previous study suggested that the splicing factor RBM39 is significantly upregulated in multiple myeloma (MM) and that its upregulation is positively associated with poor prognosis. Here, we further demonstrate that the survival and proliferation of MM cells rely on RBM39 and that RBM39 knockdown inhibits the malignant growth of MM. Indisulam, a \"molecular glue\" that mediates the proteasomal degradation of RBM39, has potent suppressive effects on MM both in vitro and in vivo. Deletion of RBM39 results in extensively altered splicing, with mis-splicing of MEK5 verified to inhibit the malignant growth of MM. Full-length MEK5 plays a vital role in maintaining MM cell survival, whereas aberrant MEK5 isoforms with exon loss exhibit loss of function and a propensity for proteasomal degradation. Targeting RBM39 or MEK5 synergistically increases the cytotoxicity of bortezomib in MM cells via the inhibition of p65. Our study validates the specific mechanism of RBM39 in MM, providing an approach for broader targeting and optimized therapeutic strategies for MM.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572169","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":"Interplay between iron metabolism, inflammation, and EPO-ERFE-Hepcidin axis in RDEB-associated chronic anemia.","authors":"Lucía Quintana-Castanedo, Rocío Maseda, Isabel Pérez-Conde, Nora V Butta, Elena Monzón-Manzano, Paula Acuña-Butta, María Gema Crespo, Antonio Buño-Soto, Eva Jiménez, Jaris Valencia, María Del Carmen de Arriba, Pilar Zuluaga, Raúl de Lucas, Marcela Del Río, Ángeles Vicente, María José Escámez, Rosa Sacedon","doi":"10.1182/bloodadvances.2024015271","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015271","url":null,"abstract":"<p><p>Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genodermatosis characterized by severe cutaneous and mucosal fragility, and frequently complicated by multifactorial chronic anemia that responds poorly to conventional therapies. This cross-sectional study investigates the factors contributing to anemia in RDEB by analyzing a representative cohort, that was stratified by disease severity, anemia and iron status, to examine their hematological parameters, cytokine profile and erythropoietin (EPO)-erythroferrone (ERFE)-hepcidin axis. Anemia was present in 50% of the cohort. Hemoglobin levels showed a strong negative correlation with the percentage of body surface area affected and C-reactive protein levels (CRP), identifying these as anemia risk factors in RDEB. Moderate-severe inflammation (CRP≥15mg/L) was observed in all anemics, but no specific cytokine profile was linked with anemia risk due to variability in IL6, IL1β, IL10, TNF, and IFN-γ levels. The regulation of the EPO-ERFE-hepcidin axis showed discrepancies with the patterns expected based on patients' anemia severity and iron status. According to reticulocyte production index, an inadequate bone marrow response was observed in 90% of anemics, irrespective of EPO levels. Patients with functional or true iron deficiency had higher ERFE levels, though ERFE showed no consistent correlation with EPO and was elevated in both anemic and non-anemic patients. Elevated hepcidin was primarily linked to the highest ferritin levels mostly in patients with a history of iron infusions and/or transfusions. These findings highlight the need for personalized, targeted approaches that address the complex interplay between inflammation and iron dysregulation, to improve anemia management in RDEB and other chronic inflammatory conditions.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143555836","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":"Binding of RHOA G17V to p300 enhances its HAT activity: a new mechanism of epigenetic deregulation in TFH lymphoma.","authors":"David Vallois, Mélanie Juilland, Kalliopi Ioannidou, Francois Lemonnier, Edoardo Missiaglia, Bettina Bisig, Margot Thome, Laurence L de Leval","doi":"10.1182/bloodadvances.2024014671","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024014671","url":null,"abstract":"<p><p>The RHOA G17V mutation is highly recurrent in follicular helper T-cell (TFH) lymphoma of the angioimmunoblastic type (AITL) (60-70% of cases) and frequently associated with mutations in other T-cell receptor signaling genes, including CD28. Here, we sought to elucidate how RHOA and CD28 variants may work in concert to sustain T-cell activation by generating stable Jurkat T-cell lines expressing wild type (wt) RHOA or RHOA G17V with wt CD28 or CD28 T195P. Concomitant expression of RHOA G17V and CD28 T195P induced significantly higher levels of interleukin 2 (IL-2) production and NFAT and AP1 transcriptional activities than either variant alone upon T-cell activation with agonistic anti-CD3 and anti-CD28 antibodies. We identified the histone acetyltransferase p300 as a major interacting partner of RHOA G17V in our model and human primary T cells. p300 inhibition abolished the increased IL-2 secretion induced by CD3/CD28 stimulation in cells expressing RHOA G17V and/or CD28 T195P. Chromatin immunoprecipitations and immunofluorescence staining revealed an increase of p300-specific H3K18ac and H3K27ac marks at the IL-2 promoter and at the whole genome level, respectively, in cells expressing RHOA G17V. Finally, immunofluorescence staining of tumor samples from four AITL patients carrying RHOA G17V variant and four AITL patients carrying wild-type RHOA showed that neoplastic TFH cells with RHOA G17V have increased H3K18ac and H3K27ac levels as compared to non-neoplastic T cells. Collectively, these findings uncover a new mechanism of action by which RHOA G17V potentiates CD28 T195P-induced NFAT and AP1 transcriptional activities by enhancing p300 histone acetyltransferase activity (HAT) and expand the notion that epigenetic deregulation contributes to the pathogenesis of TFH lymphomas.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527918","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":"Estrogen Receptor Βeta Stimulation as a Possible Novel Therapeutic Target for Cutaneous T-Cell Lymphoma.","authors":"Deniz Özistanbullu, Raphael Wilhelm, Gabi Reichenbach, Monika Doll, Karola Bahrami, Nadja Zöller, Frank Schnütgen, Anke König, Theresia Scheller, Lars Winkler, Pascal Spahn, Manuel Jaeger, Jan P Nicolay, Josef M Pfeilschifter, Bastian Schilling, Roland Kaufmann, Alexander Koch, Stefan Kippenberger, Johannes Kleemann, Markus Meissner","doi":"10.1182/bloodadvances.2024015132","DOIUrl":"https://doi.org/10.1182/bloodadvances.2024015132","url":null,"abstract":"<p><p>Cutaneous T-cell lymphomas (CTCL), including mycosis fungoides (MF) and Sézary syndrome (SS), are rare hematological malignancies with limited curative treatment options. Despite early-stage responsiveness, these malignancies often relapse in advanced stages, highlighting the need for novel, durable therapies. As other non-Hodgkin lymphoma (NHL) MF and SS have a greater incidence rate in males than females. The endocrine contribution to this gender difference is unknown. Although several studies could show a potential role of ERβ on NHL lymphomagenesis, its impact on CTCL development is unknown. In this study, we investigated LY500307, a selective ERβ agonist, as a potential treatment for CTCL. Our results show that LY500307 selectively reduced the viability of CTCL cells, sparing non-cancerous skin cells. LC-MS/MS analysis revealed that CTCL cells accumulated significantly higher concentrations of LY500307 compared to normal skin cells, likely contributing to its selective cytotoxicity. Mechanistically, LY500307 induced apoptosis, G2/M cell cycle arrest, and increased sensitivity to chemotherapeutic agents, particularly MMAE. Furthermore, LY500307 treatment significantly reduced tumor growth in a CTCL xenograft mouse model without notable toxicity. These findings suggest LY500307 as a promising therapeutic agent for CTCL, warranting further clinical investigation, including the potential for topical applications.</p>","PeriodicalId":9228,"journal":{"name":"Blood advances","volume":" ","pages":""},"PeriodicalIF":7.4,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143527922","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}