Cell Reports MedicinePub Date : 2024-10-15Epub Date: 2024-09-26DOI: 10.1016/j.xcrm.2024.101749
Marianna Decet, Patrick Scott, Sabine Kuenen, Douja Meftah, Jef Swerts, Carles Calatayud, Sandra F Gallego, Natalie Kaempf, Eliana Nachman, Roman Praschberger, Nils Schoovaerts, Chris C Tang, David Eidelberg, Samir Al Adawi, Abdullah Al Asmi, Ramachandiran Nandhagopal, Patrik Verstreken
{"title":"A candidate loss-of-function variant in SGIP1 causes synaptic dysfunction and recessive parkinsonism.","authors":"Marianna Decet, Patrick Scott, Sabine Kuenen, Douja Meftah, Jef Swerts, Carles Calatayud, Sandra F Gallego, Natalie Kaempf, Eliana Nachman, Roman Praschberger, Nils Schoovaerts, Chris C Tang, David Eidelberg, Samir Al Adawi, Abdullah Al Asmi, Ramachandiran Nandhagopal, Patrik Verstreken","doi":"10.1016/j.xcrm.2024.101749","DOIUrl":"10.1016/j.xcrm.2024.101749","url":null,"abstract":"<p><p>Synaptic dysfunction is recognized as an early step in the pathophysiology of parkinsonism. Several genetic mutations affecting the integrity of synaptic proteins cause or increase the risk of developing disease. We have identified a candidate causative mutation in synaptic \"SH3GL2 Interacting Protein 1\" (SGIP1), linked to early-onset parkinsonism in a consanguineous Arab family. Additionally, affected siblings display intellectual, cognitive, and behavioral dysfunction. Metabolic network analysis of [<sup>18</sup>F]-fluorodeoxyglucose positron emission tomography scans shows patterns very similar to those of idiopathic Parkinson's disease. We show that the identified SGIP1 mutation causes a loss of protein function, and analyses in newly created Drosophila models reveal movement defects, synaptic transmission dysfunction, and neurodegeneration, including dopaminergic synapse loss. Histology and correlative light and electron microscopy reveal the absence of synaptic multivesicular bodies and the accumulation of degradative organelles. This research delineates a putative form of recessive parkinsonism, converging on defective synaptic proteostasis and opening avenues for diagnosis, genetic counseling, and treatment.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342516","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}
Cell Reports MedicinePub Date : 2024-10-15Epub Date: 2024-09-27DOI: 10.1016/j.xcrm.2024.101750
Wenhua Liang, Jinsheng Tao, Chao Cheng, Haitao Sun, Zhujia Ye, Shuangxiu Wu, Yubiao Guo, Jiaqing Zhang, Qunqing Chen, Dan Liu, Lunxu Liu, Hui Tian, Lin Teng, Nanshan Zhong, Jian-Bing Fan, Jianxing He
{"title":"A clinically effective model based on cell-free DNA methylation and low-dose CT for risk stratification of pulmonary nodules.","authors":"Wenhua Liang, Jinsheng Tao, Chao Cheng, Haitao Sun, Zhujia Ye, Shuangxiu Wu, Yubiao Guo, Jiaqing Zhang, Qunqing Chen, Dan Liu, Lunxu Liu, Hui Tian, Lin Teng, Nanshan Zhong, Jian-Bing Fan, Jianxing He","doi":"10.1016/j.xcrm.2024.101750","DOIUrl":"10.1016/j.xcrm.2024.101750","url":null,"abstract":"<p><p>Accurate, non-invasive, and cost-effective tools are needed to assist pulmonary nodule diagnosis and management due to increasing detection by low-dose computed tomography (LDCT). We perform genome-wide methylation sequencing on malignant and non-malignant lung tissues and designed a panel of 263 differential DNA methylation regions, which is used for targeted methylation sequencing on blood cell-free DNA (cfDNA) in two prospectively collected and retrospectively analyzed multicenter cohorts. We develop and optimize an integrative model for risk stratification of pulmonary nodules based on 40 cfDNA methylation biomarkers, age, and five simple computed tomography (CT) imaging features using machine learning approaches and validate its good performance in two cohorts. Using the two-threshold strategy can effectively reduce unnecessary invasive surgeries, overtreatment costs, and injury for patients with benign nodules while advising immediate treatment for patients with lung cancer, which can potentially improve the overall diagnosis of lung cancer following LDCT/CT screening.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142342572","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":"Thymosin α1 reverses oncolytic adenovirus-induced M2 polarization of macrophages to improve antitumor immunity and therapeutic efficacy.","authors":"Kua Liu, Lingkai Kong, Huawei Cui, Louqian Zhang, Qilei Xin, Yan Zhuang, Ciliang Guo, Yongzhong Yao, Jinqiu Tao, Xiaosong Gu, Chunping Jiang, Junhua Wu","doi":"10.1016/j.xcrm.2024.101751","DOIUrl":"10.1016/j.xcrm.2024.101751","url":null,"abstract":"<p><p>Although oncolytic adenoviruses are widely studied for their direct oncolytic activity and immunomodulatory role in cancer immunotherapy, the immunosuppressive feedback loop induced by oncolytic adenoviruses remains to be studied. Here, we demonstrate that type V adenovirus (ADV) induces the polarization of tumor-associated macrophages (TAMs) to the M2 phenotype and increases the infiltration of regulatory T cells (Tregs) in the tumor microenvironment (TME). By selectively compensating for these deficiencies, thymosin alpha 1 (Tα1) reprograms \"M2-like\" TAMs toward an antitumoral phenotype, thereby reprogramming the TME into a state more beneficial for antitumor immunity. Moreover, ADV<sup>Tα1</sup> is constructed by harnessing the merits of all the components for the aforementioned combinatorial therapy. Both exogenously supplied and adenovirus-produced Tα1 orchestrate TAM reprogramming and enhance the antitumor efficacy of ADV via CD8<sup>+</sup> T cells, showing promising prospects for clinical translation. Our findings provide inspiration for improving oncolytic adenovirus combination therapy and designing oncolytic engineered adenoviruses.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142364579","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}
Cell Reports MedicinePub Date : 2024-10-15Epub Date: 2024-10-03DOI: 10.1016/j.xcrm.2024.101756
Yi-Ze Li, Ru-Rong Ji
{"title":"Gene therapy for chronic pain management.","authors":"Yi-Ze Li, Ru-Rong Ji","doi":"10.1016/j.xcrm.2024.101756","DOIUrl":"10.1016/j.xcrm.2024.101756","url":null,"abstract":"<p><p>Despite significant advances in identifying molecular targets for chronic pain over the past two decades, many remain difficult to target with traditional methods. Gene therapies such as antisense oligonucleotides (ASOs), RNA interference (RNAi), CRISPR, and virus-based delivery systems have played crucial roles in discovering and validating new pain targets. While there has been a surge in gene therapy-based clinical trials, those focusing on pain as the primary outcome remain uncommon. This review examines various gene therapy strategies, including ASOs, small interfering RNA (siRNAs), optogenetics, chemogenetics, and CRISPR, and their delivery methods targeting primary sensory neurons and non-neuronal cells, including glia and chondrocytes. We also explore emerging gene therapy tools and highlight gene therapy's clinical potential in pain management, including trials targeting pain-related diseases. Advances in single-cell analysis of sensory neurons and non-neuronal cells, along with the development of new delivery tools, are poised to accelerate the application of gene therapy in pain medicine.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375211","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":"Clinical-proteomic classification and precision treatment strategy of chordoma.","authors":"Huabin Yin, Jinbo Hu, Jianxuan Gao, Tong Su, Jiali Jin, Cong Jiang, Wenxuan Yin, Xiaowen Xu, Zhengyan Chang, Wei Sun, Zhengdong Cai, Wang Zhou, Ping Wang, Jun Lin, Dianwen Song, Tong Meng","doi":"10.1016/j.xcrm.2024.101757","DOIUrl":"10.1016/j.xcrm.2024.101757","url":null,"abstract":"<p><p>Chordoma is a rare and heterogeneous mesenchymal malignancy, with distinct clinical and biological behaviors. Till now, its comprehensive clinical-molecular characteristics and accurate molecular classification remain obscure. In this research, we enroll 102 patients with chordoma and describe their clinical, imageological, and histopathological features. Through tandem mass tag-based proteomic analysis and nonnegative matrix factorization clustering, we classify chordoma into three molecular subtypes: bone microenvironment-dominant, mesenchymal-derived, and mesenchymal-to-epithelial transition-mediated pattern. The three subtypes exhibit discrete clinical prognosis and distinct biological attributes of osteoclastogenesis and immunogenicity, oxidative phosphorylation, and receptor tyrosine kinase activation, suggesting targeted therapeutic strategies of denosumab, S-Gboxin, and anlotinib, respectively. Notably, these approaches demonstrate positive treatment outcomes for each subtype in vitro and in vivo. Altogether, this work sheds light on the clinical-proteomic characteristics of chordoma and provides a candidate precision treatment strategy for chordoma according to molecular classification, underscoring their potential for clinical application.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379156","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}
Cell Reports MedicinePub Date : 2024-10-15Epub Date: 2024-10-04DOI: 10.1016/j.xcrm.2024.101775
Wanglong Gou, Huijun Wang, Chang Su, Yuanqing Fu, Xinyu Wang, Chang Gao, Menglei Shuai, Zelei Miao, Jiguo Zhang, Xiaofang Jia, Wenwen Du, Ke Zhang, Bing Zhang, Ju-Sheng Zheng
{"title":"The temporal dynamics of the gut mycobiome and its association with cardiometabolic health in a nationwide cohort of 12,641 Chinese adults.","authors":"Wanglong Gou, Huijun Wang, Chang Su, Yuanqing Fu, Xinyu Wang, Chang Gao, Menglei Shuai, Zelei Miao, Jiguo Zhang, Xiaofang Jia, Wenwen Du, Ke Zhang, Bing Zhang, Ju-Sheng Zheng","doi":"10.1016/j.xcrm.2024.101775","DOIUrl":"10.1016/j.xcrm.2024.101775","url":null,"abstract":"<p><p>The dynamics of the gut mycobiome and its association with cardiometabolic health remain largely unexplored. Here, we employ internal transcribed spacer (ITS) sequencing to capture the gut mycobiome composition and dynamics within a nationwide human cohort of 12,641 Chinese participants, including 1,946 participants with repeated measurements across three years. We find that the gut mycobiome is associated with cardiometabolic diseases and related biomarkers in both cross-sectional and dynamic analyses. Fungal alpha diversity indices and 19 mycobiome genera are the major contributors to the mycobiome-cardiometabolic disease link. Particularly, Saccharomyces emerges as an effect modifier of traditional risk factors in promoting type 2 diabetes risk. Further integration of multi-omics data reveals key metabolites such as γ-linolenic acid and L-valine linking the gut mycobiome to type 2 diabetes. This study advances our understanding of the potential roles of the gut mycobiome in cardiometabolic health.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379062","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}
Yuan Liu, Manendra Lankadasari, Joel Rosiene, Kofi E Johnson, Juan Zhou, Samhita Bapat, Lai-Fong L Chow-Tsang, Huasong Tian, Brooke Mastrogiacomo, Di He, James G Connolly, Harry B Lengel, Raul Caso, Elizabeth G Dunne, Cameron N Fick, Gaetano Rocco, Smita Sihag, James M Isbell, Mathew J Bott, Bob T Li, Piro Lito, Cameron W Brennan, Mark H Bilsky, Natasha Rekhtman, Prasad S Adusumilli, Marty W Mayo, Marcin Imielinski, David R Jones
{"title":"Modeling lung adenocarcinoma metastases using patient-derived organoids.","authors":"Yuan Liu, Manendra Lankadasari, Joel Rosiene, Kofi E Johnson, Juan Zhou, Samhita Bapat, Lai-Fong L Chow-Tsang, Huasong Tian, Brooke Mastrogiacomo, Di He, James G Connolly, Harry B Lengel, Raul Caso, Elizabeth G Dunne, Cameron N Fick, Gaetano Rocco, Smita Sihag, James M Isbell, Mathew J Bott, Bob T Li, Piro Lito, Cameron W Brennan, Mark H Bilsky, Natasha Rekhtman, Prasad S Adusumilli, Marty W Mayo, Marcin Imielinski, David R Jones","doi":"10.1016/j.xcrm.2024.101777","DOIUrl":"10.1016/j.xcrm.2024.101777","url":null,"abstract":"<p><p>Approximately 50% of patients with surgically resected early-stage lung cancer develop distant metastasis. At present, there is no in vivo metastasis model to investigate the biology of human lung cancer metastases. Using well-characterized lung adenocarcinoma (LUAD) patient-derived organoids (PDOs), we establish an in vivo metastasis model that preserves the biologic features of human metastases. Results of whole-genome and RNA sequencing establish that our in vivo PDO metastasis model can be used to study clonality and tumor evolution and to identify biomarkers related to organotropism. Investigation of the response of KRAS<sup>G12C</sup> PDOs to sotorasib demonstrates that the model can examine the efficacy of treatments to suppress metastasis and identify mechanisms of drug resistance. Finally, our PDO model cocultured with autologous peripheral blood mononuclear cells can potentially be used to determine the optimal immune-priming strategy for individual patients with LUAD.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142459208","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}
Cell Reports MedicinePub Date : 2024-10-15Epub Date: 2024-10-04DOI: 10.1016/j.xcrm.2024.101759
Laura Mancin, Antonio Paoli, Sara Berry, Javier T Gonzalez, Adam J Collins, Maria Antonia Lizarraga, Joao Felipe Mota, Segata Nicola, Ian Rollo
{"title":"Standardization of gut microbiome analysis in sports.","authors":"Laura Mancin, Antonio Paoli, Sara Berry, Javier T Gonzalez, Adam J Collins, Maria Antonia Lizarraga, Joao Felipe Mota, Segata Nicola, Ian Rollo","doi":"10.1016/j.xcrm.2024.101759","DOIUrl":"10.1016/j.xcrm.2024.101759","url":null,"abstract":"<p><p>The gut microbiome plays a significant role in physiological functions such as nutrient processing, vitamin production, inflammatory response, and immune modulation, which, in turn, are important contributors to athlete health and performance. To date, the interpretation, discussion, and visualization of microbiome results of athletes are challenging, due to a lack of standard parameters and reference data for collection and comparison. The purpose of this perspective piece is to provide researchers with an easy-to-understand framework for the collection, analysis, and data management related to the gut microbiome with a specific focus on athletic populations. In the absence of a consensus on microbiome research in the sports field, we hope that these considerations serve as foundational \"best practice.\" Adherence to these standard operating procedures will accelerate the path toward improving the quality of data and ultimately our understanding of the influence of the gut microbiome in sport settings.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11514603/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379060","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}
Cell Reports MedicinePub Date : 2024-10-15Epub Date: 2024-10-04DOI: 10.1016/j.xcrm.2024.101770
Gui Ma, Ang Gao, Jiani Chen, Peng Liu, Rakesh Sarda, Jessica Gulliver, Yidan Wang, Carstyn Joiner, Mingshan Hu, Eui-Jun Kim, Herman Yeger, Hau D Le, Xiang Chen, Wan-Ju Li, Wei Xu
{"title":"Modeling high-risk Wilms tumors enables the discovery of therapeutic vulnerability.","authors":"Gui Ma, Ang Gao, Jiani Chen, Peng Liu, Rakesh Sarda, Jessica Gulliver, Yidan Wang, Carstyn Joiner, Mingshan Hu, Eui-Jun Kim, Herman Yeger, Hau D Le, Xiang Chen, Wan-Ju Li, Wei Xu","doi":"10.1016/j.xcrm.2024.101770","DOIUrl":"10.1016/j.xcrm.2024.101770","url":null,"abstract":"<p><p>Wilms tumor (WT) is the most common pediatric kidney cancer treated with standard chemotherapy. However, less-differentiated blastemal type of WT often relapses. To model the high-risk WT for therapeutic intervention, we introduce pluripotency factors into WiT49, a mixed-type WT cell line, to generate partially reprogrammed cells, namely WiT49-PRCs. When implanted into the kidney capsule in mice, WiT49-PRCs form kidney tumors and develop both liver and lung metastases, whereas WiT49 tumors do not metastasize. Histological characterization and gene expression signatures demonstrate that WiT49-PRCs recapitulate blastemal-predominant WTs. Moreover, drug screening in isogeneic WiT49 and WiT49-PRCs leads to the identification of epithelial- or blastemal-predominant WT-sensitive drugs, whose selectivity is validated in patient-derived xenografts (PDXs). Histone deacetylase (HDAC) inhibitors (e.g., panobinostat and romidepsin) are found universally effective across different WT and more potent than doxorubicin in PDXs. Taken together, WiT49-PRCs serve as a blastemal-predominant WT model for therapeutic intervention to treat patients with high-risk WT.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513831/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379158","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}
Cell Reports MedicinePub Date : 2024-10-15Epub Date: 2024-10-03DOI: 10.1016/j.xcrm.2024.101762
Hua Yang, Yang Xun, Yali Shen, Hongtao Wang, Yu Tao, Huihan Wang, Xinyue Zhang, Rongqiu Liu, Huarong Yu, Li Wei, Jinsong Yan, Xiaoyu Zhu, Hua You
{"title":"A simplified and robust risk stratification model for stem cell transplantation in pediatric acute myeloid leukemia.","authors":"Hua Yang, Yang Xun, Yali Shen, Hongtao Wang, Yu Tao, Huihan Wang, Xinyue Zhang, Rongqiu Liu, Huarong Yu, Li Wei, Jinsong Yan, Xiaoyu Zhu, Hua You","doi":"10.1016/j.xcrm.2024.101762","DOIUrl":"10.1016/j.xcrm.2024.101762","url":null,"abstract":"<p><p>The efficacy of stem cell transplantation (SCT) in pediatric acute myeloid leukemia (pAML) remains unsatisfactory due to the limitations of existing prognostic models in predicting efficacy and selecting suitable candidates. This study aims to develop a cytomolecular risk stratification-independent prognostic model for SCT in pAML patients at CR1 stage. The pAML SCT model, based on age, KMT2A rearrangement (KMT2A-r), and minimal residual disease at end of course 1 (MRD1), effectively classifies patients into low-, intermediate-, and high-risk groups. We validate the effectiveness in an internal validation cohort and in four external validation cohorts, consisting of different graft sources and donors. Moreover, by incorporating the FMS-like tyrosine kinase 3/internal tandem duplication (FLT3/ITD) allelic ratio, the pAML SCT model is refined, enhancing its ability to effectively select suitable candidates. We develop a simple and robust risk stratification model for pAML patients undergoing SCT, to aid in risk stratification and inform pretransplant decision-making at CR1 stage.</p>","PeriodicalId":9822,"journal":{"name":"Cell Reports Medicine","volume":null,"pages":null},"PeriodicalIF":11.7,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375209","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}
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