JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献_第10页

Differential molecular characterization of human papillomavirus-associated oropharyngeal squamous cell carcinoma and its prognostic value 人类乳头瘤病毒相关口咽鳞状细胞癌的分子特征差异及其预后价值

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-13 DOI: 10.1111/jcmm.70073

Huanhuan Wang, Qihe Zhang, Zhuangzhuang Zheng, Ying Xin, Xin Jiang

{"title":"Differential molecular characterization of human papillomavirus-associated oropharyngeal squamous cell carcinoma and its prognostic value","authors":"Huanhuan Wang, Qihe Zhang, Zhuangzhuang Zheng, Ying Xin, Xin Jiang","doi":"10.1111/jcmm.70073","DOIUrl":"https://doi.org/10.1111/jcmm.70073","url":null,"abstract":"Human papillomavirus (HPV) infection is a causative factor in the occurrence and progression of oropharyngeal squamous cell carcinoma (OPSCC). In recent years, clinical studies have found that HPV-positive OPSCC patients may present a better prognosis than HPV-negative patients, yet the underlying causes are unclear. This study aimed to investigate the relevance of HPV infection and the prognosis of OPSCC. On this basis, we aimed to establish a prediction model to accurately predict the prognosis and guide clinical practice. We analysed the records of 233 patients with OPSCC. Cox regression was applied to identify factors associated with survival. Moreover, variables with significant discrepancies were integrated into a nomogram model to predict prognosis. The results showed that HPV was an independent prognostic factor for OS and PFS. Immunoglobulin Heavy Constant Mu (IGHM) mRNA was significantly upregulated in patients with HPV-positive OPSCC. Crucially, IGHM expression was associated with better prognosis. The receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis both confirmed that the prognostic model exhibits good performance. In summary, HPV infection were independent prognostic factors for OPSCC. IGHM may be the key contributors to the prognostic differences in HPV-associated OPSCC. This nomogram model was able to accurately predict the prognosis of patients.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 19","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the therapeutic potential of miR-146a: Targeting innate inflammation in atherosclerosis 揭示 miR-146a 的治疗潜力：针对动脉粥样硬化中的先天性炎症。

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-11 DOI: 10.1111/jcmm.70121

Azizah Puspitasari Ardinal, Alice Valeria Wiyono, Reza Ishak Estiko

{"title":"Unveiling the therapeutic potential of miR-146a: Targeting innate inflammation in atherosclerosis","authors":"Azizah Puspitasari Ardinal, Alice Valeria Wiyono, Reza Ishak Estiko","doi":"10.1111/jcmm.70121","DOIUrl":"10.1111/jcmm.70121","url":null,"abstract":"Atherosclerosis is the foremost vascular disease, precipitating debilitating complications. Although therapeutic strategies have historically focused on reducing cholesterol deposition, recent insights emphasize the pivotal role of inflammation. Innate inflammation significantly contributes to plaque instability and rupture, underscoring the need for intervention across all disease stages. Numerous studies have highlighted the therapeutic potential of targeting innate immune pathways in atherosclerosis, revealing significant advancements in understanding the molecular mechanisms underlying inflammatory processes within arterial lesions. Notably, research has demonstrated that the modulation of microRNA-146a (miR-146a) expression impacts innate inflammation, effectively halts atherosclerosis progression, and enhances plaque stability by targeting interleukin-1 receptor-associated kinase (IRAK) and activating TNF receptor-associated factor 6 (TRAF6), a signalling pathway involving toll-like receptors (TLRs). Understanding the intricate mechanisms involved is crucial. This study provides a comprehensive analysis of the evidence and underlying mechanisms through which miR-146a exerts its effects. Integrating these findings into clinical practice may herald a transformative era in managing atherosclerotic cardiovascular disease.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 19","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70121","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400413","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phenotypically plastic drug-resistant chronic myeloid leukaemia cell line displays enhanced cellular dynamics in a zebrafish xenograft model 表型可塑的耐药性慢性骨髓性白血病细胞系在斑马鱼异种移植模型中显示出更强的细胞活力。

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-11 DOI: 10.1111/jcmm.70105

Seda Baykal, Zeynep Yuce, Gunes Ozhan

{"title":"Phenotypically plastic drug-resistant chronic myeloid leukaemia cell line displays enhanced cellular dynamics in a zebrafish xenograft model","authors":"Seda Baykal, Zeynep Yuce, Gunes Ozhan","doi":"10.1111/jcmm.70105","DOIUrl":"10.1111/jcmm.70105","url":null,"abstract":"Understanding the mechanisms by which cancer cells switch between different adaptive states and evade therapeutic interventions is essential for clinical management. In this study, the in vivo cellular dynamics of a new chronic myeloid leukaemia cell line displaying altered phenotype and resistance to tyrosine kinase inhibitors were investigated in correlation with their parental cells for invasiveness/metastasis, angiogenic potential and population kinetics. We showed that the cells exhibiting drug resistance and plastic phenotype possess an increased capacity for invasion compared to their parental cells, that exposure to imatinib mesylate has the potential to enhance cellular motility and that in a leukaemic cell population, even a minority of plastic cells exhibit improved migratory ability. Furthermore, we show that these plastic cells have angiogenic and extravasation potential. The present study provides significant insights into the cellular dynamics displayed by a TKI-resistant, phenotypically plastic CML cell line, using a zebrafish (Danio rerio) xenograft model.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 19","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

LTF ameliorates cartilage endplate degeneration by suppressing calcification, senescence and matrix degradation through the JAK2/STAT3 pathway LTF通过JAK2/STAT3途径抑制钙化、衰老和基质降解，从而改善软骨终板退化。

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-11 DOI: 10.1111/jcmm.18267

Tao Li, Yuchi Liu, Jian Cao, Chongzhi Pan, Rui Ding, Jiangminghao Zhao, Jiahao Liu, Dingwen He, Jingyu Jia, Xigao Cheng

引用次数: 0

LINC00941 is a diagnostic biomarker for lung adenocarcinoma and promotes tumorigenesis through cell autophagy LINC00941 是肺腺癌的诊断生物标志物，通过细胞自噬促进肿瘤发生。

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-11 DOI: 10.1111/jcmm.70076

Qin Yang, Xi Yong, Xiaoli Chen, Rong Huang, Xiaolin Wang, Zhengmin Xu, Wei Chen

{"title":"LINC00941 is a diagnostic biomarker for lung adenocarcinoma and promotes tumorigenesis through cell autophagy","authors":"Qin Yang, Xi Yong, Xiaoli Chen, Rong Huang, Xiaolin Wang, Zhengmin Xu, Wei Chen","doi":"10.1111/jcmm.70076","DOIUrl":"10.1111/jcmm.70076","url":null,"abstract":"Non-small cell lung cancer (NSCLC) is a lethal malignancy. There is mounting evidence indicating that lncRNAs are crucial players with dual roles as both biomarkers and regulators across various cancers. It was reported that LINC00941 plays a cancer-promoting role in NSCLC. However, its impact on tumour autophagy remains poorly understood. In this study, we developed a risk assessment model and identified an autophagy-related lncRNA LINC00941, which has independent predictive and early diagnostic potential. Using RT-qPCR analysis, we confirmed the upregulation of LINC00941 in tumour tissues and cell lines of human lung adenocarcinoma (LUAD). Functional assays, such as CCK8, colony formation and xenograft models, demonstrated the cancer-promoting activity of LINC00941 both in vitro and in vivo. Further analysis using Western blotting analysis, mRFP-GFP-LC3 double fluorescence lentivirus vector and transmission electron microscopy (TEM) confirmed that the knockdown of LINC00941 triggered autophagy. These results indicate that knockdown of LINC00941 induces autophagy and impairs the proliferation of LUAD. Therefore, we propose LINC00941 as an independent biomarker for early diagnosis as well as a therapeutic target in LUAD.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 19","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70076","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-cell sequencing analysis reveals the dynamic tumour ecosystems of primary and metastatic lymph nodes in nasopharyngeal carcinoma 单细胞测序分析揭示鼻咽癌原发和转移淋巴结的动态肿瘤生态系统

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-11 DOI: 10.1111/jcmm.70137

Dahua Xu, Nihui Zhang, Yutong Shen, Dehua Zheng, Zhizhou Xu, Peihu Li, Jiale Cai, Guanghui Tian, Qingchen Wei, Hong Wang, Hongyan Jiang, Meng Cao, Bo Wang, Kongning Li

{"title":"Single-cell sequencing analysis reveals the dynamic tumour ecosystems of primary and metastatic lymph nodes in nasopharyngeal carcinoma","authors":"Dahua Xu, Nihui Zhang, Yutong Shen, Dehua Zheng, Zhizhou Xu, Peihu Li, Jiale Cai, Guanghui Tian, Qingchen Wei, Hong Wang, Hongyan Jiang, Meng Cao, Bo Wang, Kongning Li","doi":"10.1111/jcmm.70137","DOIUrl":"10.1111/jcmm.70137","url":null,"abstract":"Lymph node metastasis contributed to the leading cause and treatment failure in nasopharyngeal carcinoma (NPC). The microenvironment and the cellular communications of lymph node metastasized tumours determine the tumour progression and therapeutic effect, but the ecosystems about the lymph node metastasis (LNM) for NPC patients remain poorly characterized. Here, we integrated the transcriptomes of 47,618 single cells from eight samples related to NPC LNM. The dynamic immune ecosystems and immunosuppressive microenvironment including T cells, myeloid cells and B cells were observed in the lymph node metastatic samples compared with primary tumours. Additionally, the heterogeneity of epithelial cells was also revealed, and several clusters with expression programs that were associated with the progression-free survival of NPC patients were identified. Additionally, our data revealed the complex intercellular communications from primary to lymph node metastasis. The rewiring of CCL signalling which plays an important role in tumour metastasis was further identified. Altogether, we systematically characterized the ecosystem of NPC primary and lymph node metastasized tumours, which may shed light on the development of a therapeutic strategy to improve clinical outcomes of NPC patients with lymph node metastasis.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 19","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70137","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reactive oxygen species and aldehyde dehydrogenase 1A as prognosis and theragnostic biomarker in acute myeloid leukaemia patients 活性氧和醛脱氢酶 1A 作为急性髓性白血病患者的预后和治疗生物标志物。

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-11 DOI: 10.1111/jcmm.70011

G. Venton, J. Colle, A. Tichadou, J. Quessada, C. Baier, Y. Labiad, M. Perez, L. De Lassus, M. Loosveld, I. Arnoux, N. Abbou, I. Ceylan, G. Martin, R. Costello

{"title":"Reactive oxygen species and aldehyde dehydrogenase 1A as prognosis and theragnostic biomarker in acute myeloid leukaemia patients","authors":"G. Venton, J. Colle, A. Tichadou, J. Quessada, C. Baier, Y. Labiad, M. Perez, L. De Lassus, M. Loosveld, I. Arnoux, N. Abbou, I. Ceylan, G. Martin, R. Costello","doi":"10.1111/jcmm.70011","DOIUrl":"10.1111/jcmm.70011","url":null,"abstract":"Acute myeloid leukaemia (AML) remains a major unmet medical, despite recent progress in targeted molecular therapies. One aspect of leukaemic cell resistance to chemotherapy is the development of clones with increased capacity to respond to cellular stress and the production of reactive oxygen species (ROS), thanks in particular to a high aldehyde dehydrogenases (ALDH) 1A1/2 activity. At diagnosis, ROS level and ALDH1A1/2 activity in AML patients BM are correlated with the different ELN 2022 prognostic groups and overall survival (OS). A significant lower ALDH1A1/2 activity in BM was observed in the favourable ELN2022 subgroup compared to the intermediate and adverse group (p < 0.01). In the same way, the ROS levels were significantly lower in the favourable ELN 2022 subgroup compared to the intermediate group (p < 0.0001) and adverse group (p < 0.0002). ROShigh AML patients had a significantly lower median overall survival (OS) (8.2 months) than ROSlow patients (24.6 months) (p = 0.0368). After first-line therapy, a significant increase of ROS level (p = 0.015) and ALDH1A1/2 activity (0 = 0.0273) in leukaemic blasts was observed, especially in the refractory ones. ABD-3001, a competitive and irreversible inhibitor of ALDHs 1 and 3, can in vitro inhibit the proliferation of patient-derived leukaemic cells in accordance with redox balance. In multivariate analysis, ROS level was the most significant (p < 0.05) and the strongest predictive factor for the sensitivity of cells to ABD-3001. The safety profile of ABD-3001 is currently being assessed through the first inhuman multicenter phase 1 clinical trial “ODYSSEY” (NCT05601726) for patients with relapsed AML.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 19","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Single-cell transcriptome and chromatin accessibility mapping of upper lip and primary palate fusion 上唇和原发性腭融合的单细胞转录组和染色质可及性图谱。

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-11 DOI: 10.1111/jcmm.70128

Sini Cai, Ningbei Yin

{"title":"Single-cell transcriptome and chromatin accessibility mapping of upper lip and primary palate fusion","authors":"Sini Cai, Ningbei Yin","doi":"10.1111/jcmm.70128","DOIUrl":"10.1111/jcmm.70128","url":null,"abstract":"Cleft lip and/or primary palate (CL/P) represent a prevalent congenital malformation, the aetiology of which is highly intricate. Although it is generally accepted that the condition arises from failed fusion between the upper lip and primary palate, the precise mechanism underlying this fusion process remains enigmatic. In this study, we utilized transposase-accessible chromatin sequencing (scATAC-seq) and single-cell RNA sequencing (scRNA-seq) to interrogate lambdoidal junction tissue derived from C57BL/6J mouse embryos at critical stages of embryogenesis (10.5, 11.5 and 12.5 embryonic days). We successfully identified distinct subgroups of mesenchymal and ectodermal cells involved in the fusion process and characterized their unique transcriptional profiles. Furthermore, we conducted cell differentiation trajectory analysis, revealing a dynamic repertoire of genes that are sequentially activated or repressed during pseudotime, facilitating the transition of relevant cell types. Additionally, we employed scATAC data to identify key genes associated with the fusion process and demonstrated differential chromatin accessibility across major cell types. Finally, we constructed a dynamic intercellular communication network and predicted upstream transcriptional regulators of critical genes involved in important signalling pathways. Our findings provide a valuable resource for future studies on upper lip and primary palate development, as well as congenital defects.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 19","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70128","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

SUN1 inhibits osteogenesis and promotes adipogenesis of human adipose-derived stem cells by regulating α-tubulin and CD36 expression SUN1通过调节α-tubulin和CD36的表达，抑制人脂肪来源干细胞的成骨和促进其脂肪生成。

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-09 DOI: 10.1111/jcmm.70143

Tingyu Fan, Jinhui Zhu, Wenqing Liu, Rongmei Qu, Asmat Ullah Khan, Yulian Shi, Jiaxuan Liu, Zhitao Zhou, Chujiang Xu, Jingxing Dai, Jun Ouyang

{"title":"SUN1 inhibits osteogenesis and promotes adipogenesis of human adipose-derived stem cells by regulating α-tubulin and CD36 expression","authors":"Tingyu Fan, Jinhui Zhu, Wenqing Liu, Rongmei Qu, Asmat Ullah Khan, Yulian Shi, Jiaxuan Liu, Zhitao Zhou, Chujiang Xu, Jingxing Dai, Jun Ouyang","doi":"10.1111/jcmm.70143","DOIUrl":"10.1111/jcmm.70143","url":null,"abstract":"Sad and UNC84 domain 1 (SUN1) is a kind of nuclear envelope protein with established involvement in cellular processes, including nuclear motility and meiosis. SUN1 plays an intriguing role in human adipose-derived stem cells (hASCs) differentiation; however, this role remains largely undefined. This study was undertaken to investigate the role of SUN1 in hASCs differentiation, as well as its underlying mechanisms. Employing siRNAs, we selectively downregulated SUN1 and CD36 expression. Microtubules were depolymerized using nocodazole, and PPARγ was activated using rosiglitazone. Western blotting was performed to quantify SUN1, PPARγ, α-tubulin, CD36, OPN, and adiponectin protein expression levels. Alkaline phosphatase and Oil red O staining were used to assess osteogenesis and adipogenesis, respectively. Downregulated SUN1 expression increased osteogenesis and decreased adipogenesis in hASCs, concomitant with upregulated α-tubulin expression and downregulated CD36 expression, alongside reduced nuclear localization of PPARγ. Microtubule depolymerization increased CD36 expression. Rescue experiments indicated that microtubule depolymerization counteracted the downregulated SUN1-induced phenotypic changes. This study demonstrates that SUN1 influences the differentiation of hASCs towards osteogenic and adipogenic lineages, indicating its essential role in cell fate.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 19","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463318/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390753","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Molecular characterization and biomarker identification in paediatric B-cell acute lymphoblastic leukaemia 小儿 B 细胞急性淋巴细胞白血病的分子特征和生物标志物鉴定。

IF 5.3

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE Pub Date : 2024-10-09 DOI: 10.1111/jcmm.70126

Yu Du, Xiankai Zhang, Ming Sun, Li Yang, Fei Long, Shanshan Qi, Linlin Luo, Xiaoyan Lv, Chenxuan Wang, Xiaoying Wu, Liuqing Zhu, Qiuxiang Ou, Hao Xiong

{"title":"Molecular characterization and biomarker identification in paediatric B-cell acute lymphoblastic leukaemia","authors":"Yu Du, Xiankai Zhang, Ming Sun, Li Yang, Fei Long, Shanshan Qi, Linlin Luo, Xiaoyan Lv, Chenxuan Wang, Xiaoying Wu, Liuqing Zhu, Qiuxiang Ou, Hao Xiong","doi":"10.1111/jcmm.70126","DOIUrl":"10.1111/jcmm.70126","url":null,"abstract":"B-cell acute lymphoblastic leukaemia (B-ALL) is the most prevalent hematologic malignancy in children and a leading cause of mortality. Managing B-ALL remains challenging due to its heterogeneity and relapse risk. This study aimed to delineate the molecular features of paediatric B-ALL and explore the clinical utility of circulating tumour DNA (ctDNA). We analysed 146 patients with paediatric B-ALL who received systemic chemotherapy. The mutational landscape was profiled in bone marrow (BM) and plasma samples using next-generation sequencing. Minimal residual disease (MRD) testing on day 19 of induction therapy evaluated treatment efficacy. RNA sequencing identified gene fusions in 61% of patients, including 37 novel fusions. Specifically, the KMT2A-TRIM29 novel fusion was validated in a boy who responded well to initial therapy but relapsed after 1 year. Elevated mutation counts and maximum variant allele frequency in baseline BM were associated with significantly poorer chemotherapy response (p = 0.0012 and 0.028, respectively). MRD-negative patients exhibited upregulation of immune-related pathways (p < 0.01) and increased CD8+ T cell infiltration (p = 0.047). Baseline plasma ctDNA exhibited high mutational concordance with the paired BM samples and was significantly associated with chemotherapy efficacy. These findings suggest that ctDNA and BM profiling offer promising prognostic insights for paediatric B-ALL management.","PeriodicalId":101321,"journal":{"name":"JOURNAL OF CELLULAR AND MOLECULAR MEDICINE","volume":"28 19","pages":""},"PeriodicalIF":5.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jcmm.70126","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0