Hematology最新文献_第8页

Shikonin promotes ferroptosis though NSUN2-mediated m⁵C methylation modification of TFRC in acute myelocytic leukemia. 在急性髓细胞白血病中，紫草素通过nsun2介导的m5C甲基化修饰TFRC促进铁凋亡。

IF 2 4区医学

Hematology Pub Date : 2025-12-01 Epub Date: 2025-04-24 DOI: 10.1080/16078454.2025.2495221

Shuyu Chen, Yiqun Huang, Yinhao Liu, Liuxuan Jiang, Yuqing Chen

{"title":"Shikonin promotes ferroptosis though NSUN2-mediated m5C methylation modification of TFRC in acute myelocytic leukemia.","authors":"Shuyu Chen, Yiqun Huang, Yinhao Liu, Liuxuan Jiang, Yuqing Chen","doi":"10.1080/16078454.2025.2495221","DOIUrl":"https://doi.org/10.1080/16078454.2025.2495221","url":null,"abstract":"Shikonin (SHK), extracted from the traditional Chinese herb Lithospermum erythrorhizon, demonstrates a wide range of pharmacological activities. This study aimed to explore the role and underlying mechanisms of the 5-methylcytosine (m5C) RNA methyltransferase NOL1/NOP2/SUN domain (NSUN)2 in acute myelocytic leukemia (AML). To assess cell viability and death, we employed Cell Counting Kit-8 and propidium iodide staining. Ferroptosis-related markers were evaluated using commercial kits and Western blot analysis. The m5C levels of ferroptosis-associated mRNAs were quantified by methylated RNA immunoprecipitation (MeRIP)-qPCR. The specific m5C sites on the transferrin receptor (TFRC) mRNA were identified through a dual-luciferase reporter assay, while the interaction between NSUN2 and TFRC was investigated using RNA immunoprecipitation (RIP). The role of SHK in vivo was explored using a xenografted tumor model. Our findings revealed that SHK significantly reduced cell viability and induced cell death and ferroptosis in HL-60 and NB4 cells. Notably, SHK treatment led to an upregulation of NSUN2 expression. Inhibition of NSUN2 reversed the effects of SHK, restoring cell viability and reducing cell death and ferroptosis. Mechanistically, NSUN2 enhanced TFRC expression via m5C-dependent methylation. Overexpression of NSUN2 similarly decreased cell viability and increased cell death and ferroptosis, effects that were mitigated upon silencing of TFRC. In vivo, SHK treatment effectively suppressed tumor growth in xenografted mice. In summary, our study demonstrated that SHK promoted cell death and ferroptosis in AML by modulating NSUN2-mediated m5C methylation of TFRC. These findings provided novel insights into potential therapeutic strategies for AML.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"30 1","pages":"2495221"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143998569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dose adjusted EPOCH-R is superior to RCHOP in frontline treatment of mediastinal large B cell lymphoma. 剂量调整EPOCH-R在纵隔大B细胞淋巴瘤一线治疗中优于RCHOP。

IF 2 4区医学

Hematology Pub Date : 2025-12-01 Epub Date: 2025-06-18 DOI: 10.1080/16078454.2025.2515337

Mohammad Ma'koseh, Abeer Yaseen, Nebras Abu Abed, Omar Shahin, Alaa Abufara, Khalid Halahleh, Mohammad Al-Rwashdeh, Zaid Abdel Rahman, Ro'a Muqbel, Heba Farfoura, Akram Al-Ibraheem, Kamal Al-Rabi, Hikmat Abdel-Razeq

{"title":"Dose adjusted EPOCH-R is superior to RCHOP in frontline treatment of mediastinal large B cell lymphoma.","authors":"Mohammad Ma'koseh, Abeer Yaseen, Nebras Abu Abed, Omar Shahin, Alaa Abufara, Khalid Halahleh, Mohammad Al-Rwashdeh, Zaid Abdel Rahman, Ro'a Muqbel, Heba Farfoura, Akram Al-Ibraheem, Kamal Al-Rabi, Hikmat Abdel-Razeq","doi":"10.1080/16078454.2025.2515337","DOIUrl":"10.1080/16078454.2025.2515337","url":null,"abstract":"Introduction: Primary Mediastinal Large B Cell Lymphoma (PMLBCL) is a rare but aggressive B-cell lymphoma. This study compares the outcomes and toxicities of DA-EPOCH-R (Dose-adjusted etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin in combination with rituximab) and RCHOP-21 (rituximab, cyclophosphamide, doxorubicin, and vincristine, every 21 days) in the treatment of newly diagnosed PMLBCL.Methods: We retrospectively reviewed the medical records of adults (>18 years) diagnosed with PMLBCL and treated at our center from 2010 to 2023. Baseline characteristics were compared using chi-square and Mann Whitney U-tests. Survival outcomes were analysed using Kaplan Meier and log-rank tests.Results: Eighty-seven patients were included, with a median age of 30 years (range: 18-55), 48 patients (55.2%) received RCHOP-21, and 39 patients (44.8%) received DA-EPOCH-R. Radiotherapy was more frequent in the RCHOP-21 group (66.6% vs 15%, p < 0.001). DA-EPOCH-R achieved a higher complete metabolic response (CMR) (92% vs 69%, p = 0.007). After a median follow-up of 47.4 months, patients treated with DA-EPOCH-R had superior overall survival (OS) and progression free survival (PFS); 3-year OS rates were 94.4% vs 69.8% (p = 0.01) and the 3-year PFS rates were 86.7% vs 62.2% (p = 0.016), particularly in patients with aa-IPI >1. Post-chemotherapy delta SUV max <0.75, and <0.7 correlated with relapse and mortality, respectively. Grade III-IV anemia and non-hematological toxicities were more frequent in the DA-EPOCH-R, but no therapy-related deaths occurred.Conclusions: DA-EPOCH-R improves CMR, PFS, and OS compared to R-CHOP-21 with radiotherapy in PMLBCL, particularly in high-risk patients. Longer follow-up is needed to assess long-term toxicities.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"30 1","pages":"2515337"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144316806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Sustained response off treatment after fostamatinib in refractory immune thrombocytopenia: A series of four case reports. 福司他替尼治疗难治性免疫性血小板减少症后的持续反应：一系列四例报告。

IF 2 4区医学

Hematology Pub Date : 2025-12-01 Epub Date: 2025-02-02 DOI: 10.1080/16078454.2025.2456687

Waleed Ghanima, Francisco Javier Lucas Boronat, Valentina Carrai, Stefan Rackwitz

{"title":"Sustained response off treatment after fostamatinib in refractory immune thrombocytopenia: A series of four case reports.","authors":"Waleed Ghanima, Francisco Javier Lucas Boronat, Valentina Carrai, Stefan Rackwitz","doi":"10.1080/16078454.2025.2456687","DOIUrl":"10.1080/16078454.2025.2456687","url":null,"abstract":"Introduction: A goal of most primary immune thrombocytopenia (ITP) treatments is reducing or discontinuing treatment while maintaining a response including an absence of bleeding events. We present four cases describing treatment with the spleen tyrosine kinase (SYK) inhibitor, fostamatinib, that showed sustained response off treatment (SROT).Case presentations: Case 1 was a 66-year-old male with chronic ITP. He was pre-treated with prednisone and rituximab before being in the FIT-2 clinical trial (placebo). He received fostamatinib in the FIT-3 open-label extension for seven weeks and maintained SROT for 2.5 years. Case 2 was a 54-year-old female patient with chronic, highly refractory ITP. SROT was achieved after 6 months of fostamatinib and was maintained for more than 16 months (in remission to date). Case 3 was a 60-year-old male with chronic ITP. He was successfully treated with cycles of corticosteroids for six years prior to fostamatinib. He was treated with fostamatinib plus prednisone for approximately two months. SROT was observed in this patient for one year. Case 4 was a 67-year-old male with persistent ITP. Before fostamatinib, he was unresponsive to high-dose dexamethasone, IVIG, eltrombopag and romiplostim. After 11 months of fostamatinib, his dose was tapered for three months and ultimately discontinued. SROT was observed for more than ten months (in remission to date).Discussion: These cases emphasize that SROT is achievable with fostamatinib in complex ITP cases unresponsive to multiple previous therapies. Additional research is needed to identify the magnitude of the underlying mechanisms, and the clinical factors associated with, and potentially predictive of, SROT.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"30 1","pages":"2456687"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143079696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Splenic artery embolization for the management of severe life-threatening warm autoimmune hemolytic anemia. 脾动脉栓塞治疗严重危及生命的温热自身免疫性溶血性贫血

IF 2 4区医学

Hematology Pub Date : 2025-12-01 Epub Date: 2025-04-03 DOI: 10.1080/16078454.2025.2487365

Aya Egbaria, Naiel Bisharat

{"title":"Splenic artery embolization for the management of severe life-threatening warm autoimmune hemolytic anemia.","authors":"Aya Egbaria, Naiel Bisharat","doi":"10.1080/16078454.2025.2487365","DOIUrl":"10.1080/16078454.2025.2487365","url":null,"abstract":"Background: Urgent splenectomy is recommended for the management of highly transfusion-dependent life-threatening warm autoimmune hemolytic anemia, while for individuals unfit for surgery, splenic embolization is an alternative treatment option. However, reports on its use in this context are sparse, and data on patient outcomes, effectiveness, and safety remain limited.Case presentation: A 21-year-old female patient presented with severe transfusion-dependent, life-threatening, warm autoimmune hemolytic anemia that was unresponsive to steroids and rituximab, reaching a nadir of 2.3 g/dL. Due to the severity of the anemia, she was unfit for surgery and therefore she underwent embolization of the lower two-thirds of the spleen parenchyma. Within 24 h after embolization, her hemoglobin level increased to 4.9 g/dL. A literature search yielded eight other reports describing the use of splenic embolization in severe warm autoimmune hemolytic anemia. No procedure-related deaths were reported. While some complications may require invasive interventions (e.g. splenic abscess drainage, splenectomy), the improvement in blood counts following splenic embolization often facilitated safer conditions for these procedures.Conclusion: Based on this report and review of the literature, the use of splenic embolization in cases of transfusion-dependent, life-threatening, warm autoimmune hemolytic anemia is safe and is associated with marked improvement in hemoglobin levels.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"30 1","pages":"2487365"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Impaired LTB4-induced neutrophil chemotactic directionality in myelodysplastic neoplasms patients. 骨髓增生异常肿瘤患者ltb4诱导的中性粒细胞趋化方向性受损。

IF 2 4区医学

Hematology Pub Date : 2025-12-01 Epub Date: 2025-04-01 DOI: 10.1080/16078454.2025.2483551

Xinyan Xie, Yumei Liu, Liyan Yang, Zhe Zhang, Hongzhao Li, Wei Zhang, Hong Liu, Huaquan Wang, Zonghong Shao

{"title":"Impaired LTB4-induced neutrophil chemotactic directionality in myelodysplastic neoplasms patients.","authors":"Xinyan Xie, Yumei Liu, Liyan Yang, Zhe Zhang, Hongzhao Li, Wei Zhang, Hong Liu, Huaquan Wang, Zonghong Shao","doi":"10.1080/16078454.2025.2483551","DOIUrl":"10.1080/16078454.2025.2483551","url":null,"abstract":"Objectives: Myelodysplastic neoplasm (MDS) patients are at a high risk of infections, contributing significantly to morbidity and mortality. While neutrophil dysfunction is considered a primary factor, specific functional defects remain elusive.Methods: We conducted a comprehensive study involving 90 participants, including controls and de novo MDS patients. We utilized the TAXIScan-FL system to evaluate neutrophil chemotaxis towards leukotriene B4 (LTB4). The global reactive oxygen species (ROS) production by neutrophils were measured by chemiluminescence assay, neutrophil alkaline phosphatase (NAP) was evaluated by enzymatic staining.Results: MDS patients, irrespective of absolute neutrophil count (ANC) levels, exhibited elevated empirical antimicrobial therapy (EAT) rate compared to controls. Neutrophil migration towards LTB4 was notably impaired, demonstrating reduced velocity and directionality. Interestingly, MDS patients with high ANC still displayed poor directionality and slower migration. MDS patients also had compromised ROS and NAP activity. A noteworthy correlation was observed between EAT rate and chemotactic directionality parameters.Conclusion: MDS patients face a heightened risk of infection, potentially attributed to impaired neutrophil chemotactic speed and directionality, alongside compromised ROS and NAP activity. Notably, chemotactic directionality emerged as a pivotal factor correlated with antimicrobial therapy. These insights hold significant clinical implications for managing infections in MDS patients, underscoring the importance of targeting specific neutrophil defects for more effective therapeutic strategies.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"30 1","pages":"2483551"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143763914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Efficacy and safety of decitabine combined with arsenic trioxide in elderly high-risk myelodysplastic neoplasm patients: a retrospective study. 地西他滨联合三氧化二砷治疗老年高危骨髓增生异常肿瘤的疗效和安全性回顾性研究

IF 2 4区医学

Hematology Pub Date : 2025-12-01 Epub Date: 2025-04-01 DOI: 10.1080/16078454.2025.2485493

Jianzhong Yang

{"title":"Efficacy and safety of decitabine combined with arsenic trioxide in elderly high-risk myelodysplastic neoplasm patients: a retrospective study.","authors":"Jianzhong Yang","doi":"10.1080/16078454.2025.2485493","DOIUrl":"10.1080/16078454.2025.2485493","url":null,"abstract":"Objectives: Elderly patients with high-risk myelodysplastic neoplasm (MDS) face poor outcomes with limited treatment options, often progressing to acute myeloid leukemia (AML). This study investigates the efficacy and safety of combining decitabine (DAC) with arsenic trioxide (ATO) as a novel therapeutic approach.Methods: A retrospective analysis was conducted on 120 elderly high-risk MDS patients, with 52 receiving ATO-DAC (ATO-DAC group) and 68 receiving DAC monotherapy (DAC group). Treatment outcomes were assessed through overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Adverse events were recorded and compared between the two groups.Results: The ATO-DAC group demonstrated a significantly higher ORR of 78.85% compared to 52.94% in the DAC group (P = 0.026). Median PFS was 7.5 months for the ATO-DAC group versus 5.0 months for the DAC group (P = 0.021), and median OS was 14.5 months compared to 11.5 months, respectively (P = 0.034). Although adverse events were more frequent in the ATO-DAC group, the safety profile remained manageable. These findings suggest that the ATO-DAC combination provides superior efficacy compared to DAC monotherapy.Discussion: The combination of DAC and ATO offers a promising and innovative treatment option for elderly high-risk MDS patients, enhancing response rates and survival outcomes while maintaining a manageable safety profile.Conclusion: This study underscores the clinical relevance of this regimen, warranting further investigation in prospective trials.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"30 1","pages":"2485493"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143752432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Congenital factor V deficiency in a pediatric patient causing mild hemorrhage. 先天性因子V缺乏引起轻度出血的儿科患者。

IF 2 4区医学

Hematology Pub Date : 2025-12-01 Epub Date: 2025-07-20 DOI: 10.1080/16078454.2025.2529050

Haiyue Zhang, Jun Wu

{"title":"Congenital factor V deficiency in a pediatric patient causing mild hemorrhage.","authors":"Haiyue Zhang, Jun Wu","doi":"10.1080/16078454.2025.2529050","DOIUrl":"https://doi.org/10.1080/16078454.2025.2529050","url":null,"abstract":"Background and aims: This study aimed to elucidate the phenotype and genotype of a patient (9-year-old) with coagulation factor V (FV) deficiency to enhance our understanding of this specific disorder.Methods: FV activity and antigen level were evaluated using a clotting assay and ELISA, respectively. Variations in the F5 gene were identified through DNA sequencing. The effects of the identified mutations on protein functionality were investigated using four bioinformatics tools: Expasy-ProtScale, ClustalX-2.1-win, Swiss-PdbViewer, and PyMol. These tools were applied to analyze hydrophobic properties, sequence conservation, and structural alterations.Results: The proband presented with a prolonged activated partial thromboplastin time (APTT) and a bleeding tendency. His FV activity was reduced to 22% (reference range: 50-150%). Molecular analysis of the F5 gene identified two heterozygous variants in exons: c.1177A > G (p.Lys393Glu) and c.6665A > G (p.Asp2222Gly). In silico analysis predicted the potential deleterious effects of these mutations on FV protein function and structure.Conclusion: This research identified two distinct variants in the F5 gene, including a novel variant (c.1177A > G/p.Lys393Glu). These findings elucidate the molecular mechanisms underlying the patient's FV deficiency and expand the mutational spectrum associated with this disorder.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"30 1","pages":"2529050"},"PeriodicalIF":2.0,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144667577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Budd-chiari syndrome associated with acute promyelocytic leukemia: a case and literature review. Budd-chiari综合征与急性早幼粒细胞白血病：1例及文献复习。

IF 2 4区医学

Hematology Pub Date : 2025-12-01 Epub Date: 2025-07-24 DOI: 10.1080/16078454.2025.2536390

Honglei Wang, Jing Guan, Jia Zeng, Ting Wang, Xu Lang, Rong Fu

引用次数: 0

NAT10 contributes to the progression of multiple myeloma through ac4C modification of GPR37. NAT10通过ac4C修饰GPR37参与多发性骨髓瘤的进展。

IF 1.6 4区医学

Hematology Pub Date : 2025-12-01 Epub Date: 2025-09-11 DOI: 10.1080/16078454.2025.2555779

Haiyan Liu, Xiuxiu Zhang, Qin Lu, Hui Zhang

{"title":"NAT10 contributes to the progression of multiple myeloma through ac4C modification of GPR37.","authors":"Haiyan Liu, Xiuxiu Zhang, Qin Lu, Hui Zhang","doi":"10.1080/16078454.2025.2555779","DOIUrl":"10.1080/16078454.2025.2555779","url":null,"abstract":"Background: Multiple myeloma (MM) is a malignant plasma-cell disease. Epigenetic modifications, including acetylation, are thought to contribute to tumorigenesis. N-acetyltransferase 10 (NAT10) is an important regulator of mRNA acetylation in various tumors. In this study, we explored the functions and mechanisms of action of NAT10 in MM.Methods: The expression of G protein-coupled receptor 37 (GPR37) and NAT10 was determined by qRT-PCR and western blotting, respectively. Cell proliferation was assessed using MTT and EdU assays. Cell apoptosis and cell cycle processes were analyzed using flow cytometry. Glycolysis levels were estimated using relevant commercial kits. The relationship between GPR37 and NAT10 was analyzed using the Acetylated RNA immunoprecipitation (acRIP), RIP and Actinomycin D assays. A murine xenograft model was constructed to explore the functional roles of GPR37 and NAT10 in tumor growth in vivo.Results: GPR37 was highly expressed in MM sera and cells. GPR37 knockdown inhibited MM cell proliferation, cell cycle, glycolysis, and immune escape and facilitated apoptosis in vitro. Mechanistically, NAT10 positively modulated GPR37 expression through the ac4C modification of GPR37 mRNA. Moreover, our results showed that NAT10 knockdown repressed MM cell proliferation, cell cycle, glycolysis, and immune escape; facilitated apoptosis in vitro and inhibited tumor growth in vivo by regulating GPR37 expression.Conclusion: NAT10 aggravated MM malignancy by regulating GPR37 expression. These results indicate that NAT10 and GPR37 may be novel targets for MM therapy.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"30 1","pages":"2555779"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145039958","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

4-Octyl itaconate ameliorates immune thrombocytopenia by modulating megakaryocyte autophagy and apoptosis. 衣康酸4-辛酯通过调节巨核细胞自噬和凋亡改善免疫性血小板减少症。

IF 1.6 4区医学

Hematology Pub Date : 2025-12-01 Epub Date: 2025-09-15 DOI: 10.1080/16078454.2025.2549957

Yuying Chang, Yinglan Jin, Xi Chen, Xiaomin Zhang, Yaoyao Tian, Xinyu Gao, Xiushuai Dong, Wei Wang

{"title":"4-Octyl itaconate ameliorates immune thrombocytopenia by modulating megakaryocyte autophagy and apoptosis.","authors":"Yuying Chang, Yinglan Jin, Xi Chen, Xiaomin Zhang, Yaoyao Tian, Xinyu Gao, Xiushuai Dong, Wei Wang","doi":"10.1080/16078454.2025.2549957","DOIUrl":"10.1080/16078454.2025.2549957","url":null,"abstract":"Objective: This study aimed to investigate the effects of 4-Octyl itaconate (4-OI) on immune thrombocytopenia (ITP) mice model and elucidate the underlying mechanism.Methods: An ITP mouse model was established by intraperitoneal injection of the monoclonal antibody MWReg30 and treated by 4-OI with/without chloroquine (CQ). The mice were divided into four groups: Control, ITP, ITP+4-OI and ITP+4-OI + CQ. Platelet (PLT) content was detected and bone marrow megakaryocytes were quantified using Giemsa staining. Apoptosis was evaluated by TUNEL staining, protein expression of Bax and Bcl-2 in bone marrow tissues was detected by western blotting, and megakaryocyte apoptosis ratio was assessed by flow cytometry detection of CD61+ cells. Peripheral blood mononuclear cells (PBMCs) were isolated from peripheral blood, and the mRNA expression of LC3II, Becin-1, and SQSTM1 were detected by qRT-PCR; Immunofluorescence evaluated LC3II, Beclin-1, and SQSTM1 expression in bone marrow, as well as the ratios of CD41+Beclin-1+ and CD41+LC3II+ megakaryocytes.Results: Compared to the ITP group, 4-OI treatment significantly increased PLT counts, while reduced the spleen index and bone marrow megakaryocyte numbers. 4-OI also increased the apoptosis rate of megakaryocytes by increasing Bax protein expression and reducing Bcl-2 expression in the bone marrow. LC3II and Beclin-1 expression increased in PBMCs and bone marrow tissues, whereas SQSTM1 expression decreased. Megakaryocytes exhibited reduced LC3II and Beclin-1. The autophagy inhibitor chloroquine (CQ) suppressed all the 4-OI-induced effects.Conclusion: 4-OI ameliorated ITP-induced thrombocytopenia by modulating autophagy-related proteins in megakaryocytes, inducing autophagy, and promoting apoptosis.","PeriodicalId":13161,"journal":{"name":"Hematology","volume":"30 1","pages":"2549957"},"PeriodicalIF":1.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0