Blood and Lymphatic Cancer-Targets and Therapy最新文献

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Short-Term Longitudinal Analysis of Gut Microbiota Dynamics During Anti-CD19 CAR-T Cell Therapy in Diffuse Large B-Cell Lymphoma Patients. 弥漫性大b细胞淋巴瘤患者抗cd19 CAR-T细胞治疗期间肠道微生物群动态的短期纵向分析
IF 4.9
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2026-05-01 eCollection Date: 2026-01-01 DOI: 10.2147/BLCTT.S598958
Ziyuan Shen, Xing Xing, Kang Rong, Ziyang Geng, Ning Yang, Linyan Xu, Hongfeng Ge, Wei Sang
{"title":"Short-Term Longitudinal Analysis of Gut Microbiota Dynamics During Anti-CD19 CAR-T Cell Therapy in Diffuse Large B-Cell Lymphoma Patients.","authors":"Ziyuan Shen, Xing Xing, Kang Rong, Ziyang Geng, Ning Yang, Linyan Xu, Hongfeng Ge, Wei Sang","doi":"10.2147/BLCTT.S598958","DOIUrl":"https://doi.org/10.2147/BLCTT.S598958","url":null,"abstract":"<p><strong>Purpose: </strong>Alterations in gut microbiota may influence immune response and treatment outcomes in patients with diffuse large B-cell lymphoma (DLBCL). However, the dynamics during anti-CD19 CAR-T cell therapy remain unclear.</p><p><strong>Methods: </strong>We conducted a short-term longitudinal microbiome analysis in DLBCL patients (n=12) undergoing CAR-T cell therapy targeting CD19. Stool samples were collected at baseline, 1 week, and 2 weeks post-infusion. 16S rRNA gene sequencing was used to assess microbial diversity, taxonomic composition, and functional pathways. Correlation analyses were then conducted between microbial taxa and inflammatory biomarkers.</p><p><strong>Results: </strong>Alpha diversity indices showed no statistically significant differences across time points. Beta diversity analysis revealed distinct clustering between baseline and week 1 samples in sPLS-DA, although PERMANOVA did not reach statistical significance. At the phylum level, Bacteroidota abundance significantly increased at week 2 compared with baseline (<i>P</i> = 0.008), accompanied by a marked reduction in the Firmicutes/Bacteroidota ratio. Genus-level heatmap and LEfSe analysis identified enrichment of <i>Parabacteroides</i>, and <i>Prevotella</i> at week 2, whereas baseline samples were enriched in Clostridium sensu stricto 13 and <i>Fusobacterium</i>. Functional prediction indicated that lipoic acid metabolism pathways were significantly upregulated at weeks 1 and 2 compared with baseline (both <i>P</i> < 0.05). Correlation analysis demonstrated that specific bacterial taxa, including <i>Parabacteroides</i> and <i>Prevotella</i>, were positively associated with lymphocyte counts and inversely correlated with C-reactive protein levels.</p><p><strong>Conclusion: </strong>Gut microbiota alterations following CAR-T infusion, characterized by increased Bacteroidota abundance, specific taxonomic shifts, and enhanced lipoic acid metabolism, may provide early microbial signatures for monitoring immune modulation in DLBCL patients.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"598958"},"PeriodicalIF":4.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13142727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844369","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
Poor Outcome of Pediatric Patients with Acute Lymphoblastic Leukemia Harboring Low P16 Deletion Ratio: A Post-Hoc Analysis from a Prospective Cohort. P16缺失率低的急性淋巴细胞白血病儿童患者预后差:一项前瞻性队列的事后分析
IF 4.9
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2026-04-30 eCollection Date: 2026-01-01 DOI: 10.2147/BLCTT.S592290
Kun-Yin Qiu, Xiong-Yu Liao, Hai-Lei Chen, Hong Zheng, Jian-Pei Fang, Dun-Hua Zhou
{"title":"Poor Outcome of Pediatric Patients with Acute Lymphoblastic Leukemia Harboring Low P16 Deletion Ratio: A Post-Hoc Analysis from a Prospective Cohort.","authors":"Kun-Yin Qiu, Xiong-Yu Liao, Hai-Lei Chen, Hong Zheng, Jian-Pei Fang, Dun-Hua Zhou","doi":"10.2147/BLCTT.S592290","DOIUrl":"https://doi.org/10.2147/BLCTT.S592290","url":null,"abstract":"<p><strong>Object: </strong>The prognostic significance of <i>P16 (CDKN2A)</i> deletion (<i>P16<sup>del</sup></i> ) in pediatric acute lymphoblastic leukemia (ALL) remains controversial, potentially due to the historical reliance on binary classification.</p><p><strong>Methods: </strong>In this prospective cohort study (SCCLG-ALL-2016 protocol), we analyzed 413 pediatric ALL patients. <i>P16<sup>del</sup></i> status and ratio were quantified using standardized FISH. Statistical models adjusting for key prognostic factors were performed. Piecewise linear regression identified prognostic thresholds for <i>P16<sup>del</sup></i> ratio. Survival outcomes (relapse-free survival, RFS; overall survival, OS) and interactions with minimal residual disease (MRD) were assessed.</p><p><strong>Results: </strong><i>P16<sup>del</sup></i> prevalence was 18.2% (75/413). Multivariable analysis confirmed <i>P16<sup>del</sup></i> as an independent adverse prognostic factor (RFS: <i>HR</i>=2.2, <i>p</i>=0.020; OS: <i>HR</i>=2.7, <i>p</i>=0.024). Crucially, a nonlinear dose-response relationship identified 0.8 as the critical <i>P16<sup>del</sup></i> ratio threshold: Below 0.8, each unit ratio increase conferred a 93% higher relapse/death risk (adjusted Log<i>HR</i>=1.93, <i>p</i>=0.031); above 0.8, higher ratios reduced risk by 33% (adjusted Log<i>HR</i>=0.67, <i>p</i>=0.048). Patients with low ratios (<0.8, n=37) had significantly inferior 5-year outcomes (RFS: 57.7%, OS: 72.2%) compared to high ratios (≥0.8, n=38; RFS: 88.5%, OS: 94.7%) (<i>p</i><0.001). The prognostic impact of MRD was critically dependent on <i>P16<sup>del</sup></i> ratio: Low ratio with D33 MRD+ predicted catastrophic outcomes (5-year RFS=27.8%), while high ratio patients maintained excellent survival regardless of MRD status (D33 MRD+ RFS=100%). High-ratio patients exhibited enrichment for RAS mutations (<i>p</i>=0.046).</p><p><strong>Conclusion: </strong>The identified P16 deletion ratio threshold of 0.8 may guide precision risk-adapted therapy in pediatric ALL, but its clinical utility must be validated in larger, diverse cohorts before implementation.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"592290"},"PeriodicalIF":4.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147844396","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
Enzymatic Laccase Nanoreactors Induce Apoptosis in MOLT-4-ALL Cells and Activate Prodrugs in a Synergetic Effect. 酶促漆酶纳米反应器诱导MOLT-4-ALL细胞凋亡并协同激活前药
IF 4.9
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2026-04-27 eCollection Date: 2026-01-01 DOI: 10.2147/BLCTT.S576292
Carlos A Medrano-Villagómez, Elizabeth Loredo-García, Jahaziel Gasperin-Bulbarela, Rafael Vazquez-Duhalt
{"title":"Enzymatic Laccase Nanoreactors Induce Apoptosis in MOLT-4-ALL Cells and Activate Prodrugs in a Synergetic Effect.","authors":"Carlos A Medrano-Villagómez, Elizabeth Loredo-García, Jahaziel Gasperin-Bulbarela, Rafael Vazquez-Duhalt","doi":"10.2147/BLCTT.S576292","DOIUrl":"https://doi.org/10.2147/BLCTT.S576292","url":null,"abstract":"<p><strong>Introduction: </strong>The search for novel cancer treatment strategies is of great interest. Recently, it has been reported that laccases from various sources exhibit anti-tumor effects. In addition, the use of nanometric platforms for delivering therapeutic agents at the cellular level is a promising approach for efficient cancer treatment. In this work, the cytotoxicity of <i>Coriolopsis gallica</i> laccase on human leukemia MOLT-4 cells was evaluated.</p><p><strong>Methods: </strong>Laccase was nanoconfined in a virus-like nanoparticle (VLPs) of the brome mosaic virus (BMV), and both free and nanoconfined preparations were evaluated the activation of prodrugs. The cytotoxicity was evaluated by neutral red to obtain the dose-response curve. Afterward, the death cell and mechanisms were characterized using flow cytometry of combinations of laccase (free and VLPs) with prodrugs (Doxorubicin, Irinotecan, and Procarbazine).</p><p><strong>Results: </strong>Laccase alone showed an apoptotic effect at a concentration of 0.35 μM (IC<sub>20</sub>), with a 49% of apoptotic cells at 24 hours. This effect was enhanced by the presence of doxorubicin (63.79%), irinotecan (43.44%), and procarbazine (53.27%) in the presence of both the free version (Lac) and the nano-encapsidated version (VLP-saLac). A similar effect was observed for the necroptosis population. Finally, the CI (Combination Index) was estimated by two different models, and the synergistic effect on cell death was confirmed.</p><p><strong>Discussion: </strong>The laccase pro-apoptotic effect in MOLT-4 cells has been demonstrated, increasing cytotoxicity by activating prodrugs in both free and nanoconfined forms.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"576292"},"PeriodicalIF":4.9,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134575/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821883","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
Defining High-Risk Disease Biology in Multiple Myeloma: A Narrative Review. 定义多发性骨髓瘤高危疾病生物学:叙述性回顾。
IF 4.9
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2026-04-27 eCollection Date: 2026-01-01 DOI: 10.2147/BLCTT.S586948
Mohammad Aljumaa, Hasan Hamam Refai, Yogesh Chawla, Wilson I Gonsalves
{"title":"Defining High-Risk Disease Biology in Multiple Myeloma: A Narrative Review.","authors":"Mohammad Aljumaa, Hasan Hamam Refai, Yogesh Chawla, Wilson I Gonsalves","doi":"10.2147/BLCTT.S586948","DOIUrl":"https://doi.org/10.2147/BLCTT.S586948","url":null,"abstract":"<p><p>Although modern therapies have significantly improved survival, multiple myeloma (MM) remains incurable and biologically heterogeneous, resulting in substantial variability in treatment response and outcomes. Effective risk stratification is therefore critical to guide therapy intensity, predict relapses, and inform prognosis. This review critically examines the current biological determinants of high-risk MM and their implications for treatment intensification, selection of novel therapeutic agents, and stratified clinical trial enrollment. High-risk MM is driven by three major biological determinants: (1) molecular and genomic abnormalities, including high-risk IgH translocations, del(17p), TP53 mutation, gain(1q), and high-risk gene expression signatures; (2) increased proliferative capacity, with an elevated plasma-cell S-phase fraction identifying a subgroup with markedly inferior survival independent of conventional staging; and (3) extramedullary dissemination biology, reflected by circulating tumor cells and soft-tissue extramedullary disease, both associated with marrow independence, clonal evolution, and poor outcomes. The 2024 IMS/IMWG framework integrates the genomic aspects of these biological markers and certain clinical factors into a more precisely defined disease. Complementing baseline classification, dynamic risk stratification using measurable residual disease (MRD) provides real-time prognostic refinement across the treatment course. Future advances will rely on comprehensive molecular profiling and AI-driven data integration to enable precision-guided treatment based on individualized disease biology.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"586948"},"PeriodicalIF":4.9,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13134554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821830","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
Venetoclax Plus Hypomethylating Agents for Treatment-Naïve Myelodysplastic Syndromes with Increased Blasts: A Prospective Multicenter Cohort Study. Venetoclax加低甲基化药物治疗Treatment-Naïve骨髓增生异常综合征伴原细胞增多:一项前瞻性多中心队列研究
IF 4.9
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2026-04-24 eCollection Date: 2026-01-01 DOI: 10.2147/BLCTT.S592550
Na Zhao, Lijun Zhu, Xing Hu, Juan Tong, Hongfeng Ge, Li Ye, Xijun Zhu, Can Gai, Yuhu Feng, Lei Zhang, Li Wang, Guangyu Sun, Lei Xue, Xiaoyu Zhu, Changcheng Zheng
{"title":"Venetoclax Plus Hypomethylating Agents for Treatment-Naïve Myelodysplastic Syndromes with Increased Blasts: A Prospective Multicenter Cohort Study.","authors":"Na Zhao, Lijun Zhu, Xing Hu, Juan Tong, Hongfeng Ge, Li Ye, Xijun Zhu, Can Gai, Yuhu Feng, Lei Zhang, Li Wang, Guangyu Sun, Lei Xue, Xiaoyu Zhu, Changcheng Zheng","doi":"10.2147/BLCTT.S592550","DOIUrl":"https://doi.org/10.2147/BLCTT.S592550","url":null,"abstract":"<p><strong>Purpose: </strong>Evidence supporting venetoclax combined with hypomethylating agents (HMAs) in treatment-naïve myelodysplastic syndromes with increased blasts (MDS-IB), a biologically aggressive subset with high risk of leukemic transformation, remains lacking. We conducted a prospective, multicenter cohort study to evaluate the efficacy and safety of venetoclax plus HMAs in newly diagnosed MDS-IB.</p><p><strong>Patients and methods: </strong>In this prospective, multicenter, single-arm trial conducted at six hospitals in China (August 2022-September 2024), 43 newly diagnosed adults with MDS-IB received venetoclax (ramp-up to 400 mg on days 1-14) plus azacitidine or decitabine in 28-day cycles. Dose adjustments were made for cytopenias, infections, or drug interactions. Primary endpoints were overall response rate (ORR), duration of response (DoR), and safety. Secondary endpoints included overall survival (OS) and transformation to acute myeloid leukemia. The study was registered in the Chinese Clinical Trial Registry (registration number: [ChiCTR2200055204]).</p><p><strong>Results: </strong>The ORR was 74.4% (95% CI, 58.8-86.5%), comprising 34.4% complete remission (CR), 59.4% marrow CR (mCR), and 6.3% partial response (PR). Among the thirty-two patients who got ORR, the median DoR was 8.1 months (range, 0.9-29.0). The 6-, 12-, and 24-month DoR rates were 68.8% (95% CI, 49.7-81.8%), 53.2% (95% CI, 33.7-69.4%), and 47.7% (95% CI, 27.8-65.1%), respectively. Median OS was 12.8 months, with 12- and 24-month OS rates of 62.4% (95% CI, 46.1-75.1%) and 49.3% (95% CI, 32.2-64.3%), respectively. Grade 3/4 neutropenia/febrile neutropenia occurred in 60% (26/43), and pneumonia in 16% (7/43). The median interval between cycles was 59 days (range 33-113), mainly due to hematologic toxicity.</p><p><strong>Conclusion: </strong>Venetoclax plus HMAs demonstrated promising clinical activity with manageable toxicity in newly diagnosed MDS-IB, supporting further prospective evaluation of this combination in treatment-naïve patients with increased-blast MDS.</p><p><strong>Trial registration: </strong>Chinese Clinical Trial Registry, ChiCTR2200055204, https://www.chictr.org.cn/index.html.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"592550"},"PeriodicalIF":4.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13123550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147784486","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
Prognostic Value of the Aggregate Inflammation Systemic Index (AISI) in Patients with Diffuse Large B-Cell Lymphoma: A Multicenter Retrospective Study. 弥漫性大b细胞淋巴瘤患者总体炎症系统指数(AISI)的预后价值:一项多中心回顾性研究
IF 4.9
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2026-03-31 eCollection Date: 2026-01-01 DOI: 10.2147/BLCTT.S571663
Xicheng Chen, Linyu Huang, Qiming Zhang, Xing Xing, Shuo Zhang, Chunling Wang, Ling Wang, Ziyuan Shen, Wei Sang
{"title":"Prognostic Value of the Aggregate Inflammation Systemic Index (AISI) in Patients with Diffuse Large B-Cell Lymphoma: A Multicenter Retrospective Study.","authors":"Xicheng Chen, Linyu Huang, Qiming Zhang, Xing Xing, Shuo Zhang, Chunling Wang, Ling Wang, Ziyuan Shen, Wei Sang","doi":"10.2147/BLCTT.S571663","DOIUrl":"https://doi.org/10.2147/BLCTT.S571663","url":null,"abstract":"<p><strong>Background: </strong>The aggregate index of systemic inflammation (AISI, calculated as neutrophil count × monocyte count × platelet count/lymphocyte count) reflects systemic inflammatory status; however, its prognostic role in diffuse large B-cell lymphoma (DLBCL) remains underexplored. This study aimed to investigate the prognostic value of AISI in DLBCL.</p><p><strong>Methods: </strong>A total of 1332 DLBCL patients (median age 62 years; 52.3% male) were included in this study. Patients were stratified based on AISI quartiles, and a cut-off value was determined using restricted cubic splines (RCS) analysis. The associations between AISI and Overall survival (OS) were assessed using Kaplan-Meier analysis and Cox proportional hazards models.</p><p><strong>Results: </strong>Higher AISI levels were associated with adverse clinical features, including advanced Ann Arbor stage, poor performance status, and higher-risk categories of both the IPI and the NCCN-IPI. RCS analysis revealed a nonlinear relationship between AISI and OS, with an inflection point at 261.33. Kaplan-Meier analysis demonstrated that patients with AISI > 261.33 had significantly worse OS compared to those with AISI ≤ 261.33 (<i>P</i> = 0.003). Similarly, patients in the Q4 group had poorer OS than those in the lowest two quartiles (Q1-Q2) (<i>P</i> = 0.008). In fully adjusted Cox proportional hazards models (adjusted for age, sex, Ann Arbor stage, LDH, ECOG performance status, BMI, albumin, B symptoms, bone marrow involvement, central nervous system involvement, and liver/spleen involvement), high AISI level (> 261.33) were associated with increased mortality risk (<i>HR</i> = 1.28, 95% CI: 1.04-1.57, <i>P</i> = 0.018). Subgroup analyses indicated that the prognostic impact of AISI was particularly evident among patients classified as low risk by conventional prognostic systems.</p><p><strong>Conclusion: </strong>Elevated AISI was associated with inferior OS in DLBCL patients and may potentially serve as a prognostic biomarker.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"571663"},"PeriodicalIF":4.9,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13050976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147634621","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
Crosstalk Between FOXN3 and E2F5 Reveals a Novel Tumor Suppressive Pathway in Acute Myeloid Leukemia via MAPK Signaling: Implications for Potential Future Targeted Therapy. FOXN3和E2F5之间的串音通过MAPK信号揭示了急性髓系白血病中一种新的肿瘤抑制途径:对未来潜在的靶向治疗的意义
IF 4.9
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2026-03-24 eCollection Date: 2026-01-01 DOI: 10.2147/BLCTT.S571966
Jinjing Zhang, Qiao Jiang, Tong Liu, Hong Li, Ying Liang, Xianglan Lu, Hui Pang, Shibo Li, Yan Li, Rui Zhang
{"title":"Crosstalk Between FOXN3 and E2F5 Reveals a Novel Tumor Suppressive Pathway in Acute Myeloid Leukemia via MAPK Signaling: Implications for Potential Future Targeted Therapy.","authors":"Jinjing Zhang, Qiao Jiang, Tong Liu, Hong Li, Ying Liang, Xianglan Lu, Hui Pang, Shibo Li, Yan Li, Rui Zhang","doi":"10.2147/BLCTT.S571966","DOIUrl":"10.2147/BLCTT.S571966","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the mechanism of FOXN3 in acute leukemia.</p><p><strong>Methods: </strong>ChIP-seq experiments were performed using FOXN3-specific antibodies to identify FOXN3 target genes in acute myeloid leukemia (AML). Bioinformatics analyses were conducted to determine the enrichment of biological processes and pathways related to cell cycle regulation and apoptosis among the target genes. The transcriptional regulation of the gene of interest was confirmed through RT-qPCR, Western blotting, and luciferase reporter assays. Additionally, we examined the significance of FOXN3 on the prognosis of AML patients. Functional studies were performed following the knockdown and overexpression of the target gene in AML cells. Furthermore, we investigated the interaction between FOXN3 and the target gene by co-transfecting AML cells with lentiviruses overexpressing the target gene, followed by examinations of downstream signaling pathways through RNA-seq and pathway enrichment analyses.</p><p><strong>Results: </strong>FOXN3 regulates E2F5 expression, leading to decreased mRNA and protein levels of E2F5 upon FOXN3 overexpression, though additional factors may contribute to this repression. Notably, E2F5 expression was elevated in AML patients and cell lines, correlating with unfavorable clinical outcomes. Functional investigations revealed that E2F5 functions as an oncogene in AML, promoting cell proliferation, inhibiting apoptosis, and influencing cell cycle progression. Co-transfection experiments demonstrated that E2F5 could counteract the proliferation-inhibitory effect of FOXN3. Additionally, FOXN3 was found to modulate the MAPK signaling pathway and its downstream target, EZH2.</p><p><strong>Conclusion: </strong>This study reveals a novel regulatory axis involving FOXN3 and E2F5 in AML. FOXN3 acts as a tumor suppressor by regulating E2F5 and modulating downstream MAPK signaling pathways.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"571966"},"PeriodicalIF":4.9,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13032739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147575676","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
Health Disparities in Acute Myeloid Leukemia Patients Undergoing Treatment with Tyrosine Kinase Inhibitor (TKI) Therapy Targeting FLT3, IDH1, or IDH2. 急性髓系白血病患者接受针对FLT3、IDH1或IDH2的酪氨酸激酶抑制剂(TKI)治疗的健康差异
IF 4.9
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2026-03-12 eCollection Date: 2026-01-01 DOI: 10.2147/BLCTT.S559759
Manuel R Espinoza-Gutarra, Brooke A Jarrett, Xiaoliang Wang, Anosheh Afghahi, Sejong Bae
{"title":"Health Disparities in Acute Myeloid Leukemia Patients Undergoing Treatment with Tyrosine Kinase Inhibitor (TKI) Therapy Targeting FLT3, IDH1, or IDH2.","authors":"Manuel R Espinoza-Gutarra, Brooke A Jarrett, Xiaoliang Wang, Anosheh Afghahi, Sejong Bae","doi":"10.2147/BLCTT.S559759","DOIUrl":"https://doi.org/10.2147/BLCTT.S559759","url":null,"abstract":"<p><p>Acute Myeloid Leukemia (AML) is a common hematologic neoplasm in adults and usually carries a grim prognosis. Therapy has traditionally consisted of intensive chemotherapy; however, recent advances have led to the development of Tyrosine Kinase Inhibitors (TKI) as Targeted Therapies for subtypes carrying certain mutations. While the clinical impact of these therapies has been well described, there have been no studies looking at clinical disparities among different racial/ethnic groups receiving these therapies. We leveraged an EHR-derived database to evaluate real-world outcomes in patients receiving TKIs for AML. Our study found no significant differences between real-world Event Free Survival (rwEFS) and real world Overall Survival (rwOS) across patients of different racial/ethnic groups, this suggests that when patients have access to targeted therapy outcomes across different racial/ethnic groups become more equitable.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"559759"},"PeriodicalIF":4.9,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12990797/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475727","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
Construction and Validation of an N7-Methylguanosine-Related Prognostic Model for Acute Myeloid Leukemia. 急性髓系白血病n7 -甲基鸟苷相关预后模型的构建与验证。
IF 4.9
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2026-03-11 eCollection Date: 2026-01-01 DOI: 10.2147/BLCTT.S575337
Lina Wang, Ming Li, Yaming Xi
{"title":"Construction and Validation of an N7-Methylguanosine-Related Prognostic Model for Acute Myeloid Leukemia.","authors":"Lina Wang, Ming Li, Yaming Xi","doi":"10.2147/BLCTT.S575337","DOIUrl":"https://doi.org/10.2147/BLCTT.S575337","url":null,"abstract":"<p><strong>Purpose: </strong>Increasing evidence suggests the involvement of N7-methylguanosine (m7G) in cancer biology. However, its role in acute myeloid leukemia (AML) remains unclear. Herein, bioinformatics approaches were used to obtain insights for AML risk stratification and treatment.</p><p><strong>Patients and methods: </strong>Data from TCGA-LAML, GSE114868, and GSE37642 were analyzed. Differentially expressed genes from GSE114868 were intersected with key module genes identified via weighted gene co-expression network analysis. The identified genes underwent univariate and multivariate Cox regression analyses and machine learning to identify prognostically relevant m7G-related genes (m7G-RGs). Moreover, a prognostic risk model was built and validated, and its association with immune infiltration was evaluated. Model performance was compared with the European LeukemiaNet (ELN) 2022 genetic risk stratification system. Expression levels of key genes were analyzed in GSE114868 and validated in independent clinical samples.</p><p><strong>Results: </strong>A prognostic risk model was developed based on seven m7G-RGs (<i>TM6SF1, IL1R2, MTX1, SUSD3, SLC22A4, TUBA4A, and RETN</i>). Patients with AML were stratified into high- and low-risk groups, with the low-risk group showing significantly longer overall survival. Compared with the ELN 2022 classification, the model provided significant prognostic refinement within the heterogeneous intermediate-risk subgroup. <i>IL1R2</i> and <i>TUBA4A</i> expression were significantly associated with immune cell infiltration scores. Consistent with the bioinformatics analyses, <i>TM6SF1, IL1R2, MTX1, and SLC22A4</i> expression was significantly reduced in an independent AML cohort and in patient samples compared with controls.</p><p><strong>Conclusion: </strong>We developed and validated a novel m7G-related prognostic model for AML based on seven genes. The findings suggest a potential association among m7G modification, AML prognosis, and the tumor immune microenvironment. The model showed complementary value to the ELN 2022 risk stratification by improving risk assessment among patients classified as intermediate risk. As a retrospective, computational study, prospective validation is required. The identified m7G-RGs warrant further investigation as potential biomarkers or therapeutic targets.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"575337"},"PeriodicalIF":4.9,"publicationDate":"2026-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12991311/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147475711","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
Association Between Petroleum Compounds Exposure and Risk of Childhood Leukemia: A Systematic Review. 石油化合物暴露与儿童白血病风险的关系:一项系统综述。
IF 4.9
Blood and Lymphatic Cancer-Targets and Therapy Pub Date : 2026-02-11 eCollection Date: 2026-01-01 DOI: 10.2147/BLCTT.S571340
Hossam Mohamed Hassan Soliman, Wesal Youssef Hassan, Marwa Mostafa, Mohamed Khamis Gomaa, Mohamed Hossam Soliman Jnr, Mohamed Fakhry Hussein
{"title":"Association Between Petroleum Compounds Exposure and Risk of Childhood Leukemia: A Systematic Review.","authors":"Hossam Mohamed Hassan Soliman, Wesal Youssef Hassan, Marwa Mostafa, Mohamed Khamis Gomaa, Mohamed Hossam Soliman Jnr, Mohamed Fakhry Hussein","doi":"10.2147/BLCTT.S571340","DOIUrl":"https://doi.org/10.2147/BLCTT.S571340","url":null,"abstract":"<p><p>Childhood leukemia remains a critical public health concern, necessitating comprehensive evaluations of environmental risk factors. This systematic review aims to evaluate the epidemiological evidence regarding the relationship between combined oil exposure during pregnancy and childhood and an increased risk of childhood leukemia, thereby contributing to improved overall childhood health. The review focused on children diagnosed with leukemia. Following the guidelines set forth by the Cochrane Handbook for Systematic Reviews of Interventions' instructions, we conducted a systematic review. Three databases (PubMed, Google Scholar, and Medline) were thoroughly searched to find research that was up to May 31, 2025. Two independent reviewers screened the literature by using Covidence software. The methodological quality and potential for bias in each included case-control and cohort study were systematically evaluated using the Quality Assessment Tool integrated within Covidence software. We assessed the overall quality of evidence using AMSTAR 2, a widely used instrument for critically appraising systematic reviews. In total, 13 studies were included in this review: 11 case-control and 2 cohort studies with an overall sample size of 2,808,870 individuals. Four studies indicated a statistically significant association between maternal and paternal exposure to \"gasoline, benzene, diesel exhaust, oil, mineral oil, and gas\" and an increased likelihood of childhood leukemia. One study indicated that the association with petrol compound exposure appeared stronger for acute myeloid leukemia (AML) than for acute lymphoblastic leukemia (ALL). Multiple studies reported positive associations between different petroleum compound exposures and childhood leukemia. In conclusion, the current review pointed toward an association between exposure to petrol compounds and a higher risk of childhood leukemia. Therefore, we recommend implementing stricter environmental regulations on benzene emissions and establishing evidence-based safety buffer zones between petrol stations and residential areas. Furthermore, routine air quality monitoring near these sites is essential to safeguard pediatric health.</p>","PeriodicalId":42368,"journal":{"name":"Blood and Lymphatic Cancer-Targets and Therapy","volume":"16 ","pages":"571340"},"PeriodicalIF":4.9,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12912160/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146220507","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
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