{"title":"儿童急性髓性白血病的双上睑下垂:多组学方法的风险分层和潜在的治疗策略。","authors":"Yichen Lei, Jiasi Zhang, Yaqin Wang, Aiguo Liu","doi":"10.1186/s12935-025-03824-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The evolving molecular portrait of acute myeloid leukemia (AML) has exposed previously unrecognized cell death programs that fuel disease progression and treatment resistance-uncovering untapped therapeutic potential. Recent work has uncovered disulfidptosis-a novel form of programmed cell death (PDC) triggered by glucose deprivation in SLC7A11-high AML cells-as a potential therapeutic vulnerability. However, disulfidptosis in pediatric AML (pAML) remains largely unexplored, with no comprehensive studies assessing its biological significance or clinical prognostic value.</p><p><strong>Method: </strong>Here, we systematically characterize disulfidptosis in pediatric AML through multi-omics integration. Using ssGSEA, we quantified PDC patterns across bulk and single-cell transcriptomes, revealing distinct molecular subtypes via unsupervised clustering. Machine learning deciphered the biological networks underlying disulfidptosis, while in vitro experiments were performed to further validate.</p><p><strong>Results: </strong>In this study, we demonstrated that elevated disulfidptosis scores were associated with poor prognosis and a hypermetabolic state. Notably, patients carrying different driver mutations exhibited distinct levels of disulfidptosis susceptibility. Through in vitro experiments utilizing both cell lines and primary patient-derived cells, we found that elevated expression of SLC7A11, a key regulator of disulfidptosis, correlated with chemoresistance. Furthermore, disulfidptosis signatures effectively stratified risk subgroups in pAML, revealing a novel subtype, DSP3, characterized by prominent disulfidptosis features, an immune-desert tumor microenvironment, and an unfavorable prognosis. Additionally, our in vitro experiments identified the GLUT1 inhibitor STF-31 and the mitochondrial-targeted agent darinaparsin as potential therapeutic options for DSP3 patients, and combining with conventional chemotherapy exhibited a synergistic anti-tumor effect.</p><p><strong>Conclusion: </strong>In summary, this study employed multi-omics analysis to examine the characteristics of pAML in the context of disulfidptosis, identifying a novel disulfidptosis-related subtype, aiming to provide new insights for future studies on optimizing traditional regimen based on pAML pathogenesis.</p>","PeriodicalId":9385,"journal":{"name":"Cancer Cell International","volume":"25 1","pages":"199"},"PeriodicalIF":6.0000,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131395/pdf/","citationCount":"0","resultStr":"{\"title\":\"Disulfidptosis in pediatric AML: a multi-omics approach to risk stratification and potential therapeutic strategy.\",\"authors\":\"Yichen Lei, Jiasi Zhang, Yaqin Wang, Aiguo Liu\",\"doi\":\"10.1186/s12935-025-03824-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The evolving molecular portrait of acute myeloid leukemia (AML) has exposed previously unrecognized cell death programs that fuel disease progression and treatment resistance-uncovering untapped therapeutic potential. Recent work has uncovered disulfidptosis-a novel form of programmed cell death (PDC) triggered by glucose deprivation in SLC7A11-high AML cells-as a potential therapeutic vulnerability. However, disulfidptosis in pediatric AML (pAML) remains largely unexplored, with no comprehensive studies assessing its biological significance or clinical prognostic value.</p><p><strong>Method: </strong>Here, we systematically characterize disulfidptosis in pediatric AML through multi-omics integration. Using ssGSEA, we quantified PDC patterns across bulk and single-cell transcriptomes, revealing distinct molecular subtypes via unsupervised clustering. Machine learning deciphered the biological networks underlying disulfidptosis, while in vitro experiments were performed to further validate.</p><p><strong>Results: </strong>In this study, we demonstrated that elevated disulfidptosis scores were associated with poor prognosis and a hypermetabolic state. Notably, patients carrying different driver mutations exhibited distinct levels of disulfidptosis susceptibility. Through in vitro experiments utilizing both cell lines and primary patient-derived cells, we found that elevated expression of SLC7A11, a key regulator of disulfidptosis, correlated with chemoresistance. Furthermore, disulfidptosis signatures effectively stratified risk subgroups in pAML, revealing a novel subtype, DSP3, characterized by prominent disulfidptosis features, an immune-desert tumor microenvironment, and an unfavorable prognosis. Additionally, our in vitro experiments identified the GLUT1 inhibitor STF-31 and the mitochondrial-targeted agent darinaparsin as potential therapeutic options for DSP3 patients, and combining with conventional chemotherapy exhibited a synergistic anti-tumor effect.</p><p><strong>Conclusion: </strong>In summary, this study employed multi-omics analysis to examine the characteristics of pAML in the context of disulfidptosis, identifying a novel disulfidptosis-related subtype, aiming to provide new insights for future studies on optimizing traditional regimen based on pAML pathogenesis.</p>\",\"PeriodicalId\":9385,\"journal\":{\"name\":\"Cancer Cell International\",\"volume\":\"25 1\",\"pages\":\"199\"},\"PeriodicalIF\":6.0000,\"publicationDate\":\"2025-06-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12131395/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Cell International\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s12935-025-03824-9\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Cell International","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12935-025-03824-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Disulfidptosis in pediatric AML: a multi-omics approach to risk stratification and potential therapeutic strategy.
Background: The evolving molecular portrait of acute myeloid leukemia (AML) has exposed previously unrecognized cell death programs that fuel disease progression and treatment resistance-uncovering untapped therapeutic potential. Recent work has uncovered disulfidptosis-a novel form of programmed cell death (PDC) triggered by glucose deprivation in SLC7A11-high AML cells-as a potential therapeutic vulnerability. However, disulfidptosis in pediatric AML (pAML) remains largely unexplored, with no comprehensive studies assessing its biological significance or clinical prognostic value.
Method: Here, we systematically characterize disulfidptosis in pediatric AML through multi-omics integration. Using ssGSEA, we quantified PDC patterns across bulk and single-cell transcriptomes, revealing distinct molecular subtypes via unsupervised clustering. Machine learning deciphered the biological networks underlying disulfidptosis, while in vitro experiments were performed to further validate.
Results: In this study, we demonstrated that elevated disulfidptosis scores were associated with poor prognosis and a hypermetabolic state. Notably, patients carrying different driver mutations exhibited distinct levels of disulfidptosis susceptibility. Through in vitro experiments utilizing both cell lines and primary patient-derived cells, we found that elevated expression of SLC7A11, a key regulator of disulfidptosis, correlated with chemoresistance. Furthermore, disulfidptosis signatures effectively stratified risk subgroups in pAML, revealing a novel subtype, DSP3, characterized by prominent disulfidptosis features, an immune-desert tumor microenvironment, and an unfavorable prognosis. Additionally, our in vitro experiments identified the GLUT1 inhibitor STF-31 and the mitochondrial-targeted agent darinaparsin as potential therapeutic options for DSP3 patients, and combining with conventional chemotherapy exhibited a synergistic anti-tumor effect.
Conclusion: In summary, this study employed multi-omics analysis to examine the characteristics of pAML in the context of disulfidptosis, identifying a novel disulfidptosis-related subtype, aiming to provide new insights for future studies on optimizing traditional regimen based on pAML pathogenesis.
期刊介绍:
Cancer Cell International publishes articles on all aspects of cancer cell biology, originating largely from, but not limited to, work using cell culture techniques.
The journal focuses on novel cancer studies reporting data from biological experiments performed on cells grown in vitro, in two- or three-dimensional systems, and/or in vivo (animal experiments). These types of experiments have provided crucial data in many fields, from cell proliferation and transformation, to epithelial-mesenchymal interaction, to apoptosis, and host immune response to tumors.
Cancer Cell International also considers articles that focus on novel technologies or novel pathways in molecular analysis and on epidemiological studies that may affect patient care, as well as articles reporting translational cancer research studies where in vitro discoveries are bridged to the clinic. As such, the journal is interested in laboratory and animal studies reporting on novel biomarkers of tumor progression and response to therapy and on their applicability to human cancers.