Leukemia research最新文献_第8页

IGF2BP3 promotes acute myeloid leukemia cell progression by regulating Semaphorin 4D stability in an m6A-dependent manner IGF2BP3通过m6a依赖的方式调节Semaphorin 4D的稳定性，从而促进急性髓系白血病细胞的进展。

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-10 DOI: 10.1016/j.leukres.2025.108119

Juan Li , Shulan Shi , Kefu Zhu , Linyang Zhe , Tianle Lu , Quanzhen Deng , Qingfang Li , Qiuling Hou , Tilong Huang , Qiangming Sun , Ming Yu , Hongchao Jiang

Background

Our previous findings indicate Semaphorin 4D (Sema4D) as a potential pediatric leukemia biomarker, promoting leukemogenesis via PI3K/AKT and ERK pathways, but its upstream regulatory mechanisms remain unclear. This study was conducted to explore the potential regulatory relationship between Insulin growth factor 2 mRNA binding protein 3 (IGF2BP3) and Sema4D in acute myeloid leukemia (AML).

Methods

The expression levels of Sema4D and IGF2BP3 were analyzed in PBMCs from 41 newly diagnosed patients with pediatric acute myeloid leukemia (AML) and 35 healthy pediatric donors who presented no history of leukemia using western blotting and qRT-PCR. IGF2BP3 overexpression and knockdown models were established in Kasumi-1 and HL-60 cells via lentiviral infection. Cell proliferation, apoptosis, and cell cycle distribution were assessed using CCK-8 and flow cytometry. The stability of Sema4D mRNA and m6A methylation levels were evaluated via mRNA stability assay and qPCR.

Results

This study discovered that Sema4D and IGF2BP3 were overexpressed in the peripheral blood mononuclear cells (PBMCs) of AML patients, and their expression levels were positively correlated. IGF2BP3 overexpression enhanced cell proliferation and cell cycle progression, and inhibited apoptosis in AML cells, while knockdown had the opposite effect. Mechanistic exploration revealed that IGF2BP3 enhances the stability of Sema4D mRNA through m6A-dependent mechanisms.

Conclusion

In this study, we demonstrate that the IGF2BP3/Sema4D axis is a crucial regulator in AML development, driving cell proliferation and survival through post-transcriptional regulation of Sema4D by IGF2BP3 in an m6A-dependent manner. Our findings highlight the potential of targeting this axis as a therapeutic strategy for AML treatment.

背景：我们之前的研究结果表明，信号蛋白4D （Sema4D）是一种潜在的儿科白血病生物标志物，通过PI3K/AKT和ERK途径促进白血病的发生，但其上游调控机制尚不清楚。本研究旨在探讨胰岛素生长因子2 mRNA结合蛋白3 （IGF2BP3）与Sema4D在急性髓性白血病（AML）中的潜在调控关系。方法：应用western blotting和qRT-PCR分析41例小儿急性髓性白血病（AML）新诊断患者和35例无白血病病史的健康儿童供者外周血中Sema4D和IGF2BP3的表达水平。通过慢病毒感染在Kasumi-1和HL-60细胞中建立IGF2BP3过表达和低表达模型。采用CCK-8和流式细胞术评估细胞增殖、凋亡和细胞周期分布。通过mRNA稳定性测定和qPCR评估Sema4D mRNA和m6A甲基化水平的稳定性。结果：本研究发现，Sema4D和IGF2BP3在AML患者外周血单个核细胞（PBMCs）中过表达，且表达水平呈正相关。IGF2BP3过表达增强AML细胞增殖和细胞周期进程，抑制细胞凋亡，而敲低则相反。机制探索表明，IGF2BP3通过m6a依赖性机制增强Sema4D mRNA的稳定性。结论：在本研究中，我们证明了IGF2BP3/Sema4D轴在AML发展中是一个重要的调节因子，通过IGF2BP3以m6a依赖的方式转录后调节Sema4D，驱动细胞增殖和存活。我们的发现强调了靶向这一轴作为AML治疗策略的潜力。

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引用次数: 0

Infectious complications in pediatric acute lymphoblastic leukemia treatment: A comparison of ALL-IC BFM 2009 vs. modified St. Jude total XV in a single-center retrospective cohort study 儿科急性淋巴细胞白血病治疗中的感染并发症：一项单中心回顾性队列研究中ALL-IC BFM 2009与改良St. Jude total XV的比较

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-08 DOI: 10.1016/j.leukres.2025.108120

Dilara Unal , Fatma Gumruk , Selin Aytac , Baris Kuskonmaz , Muhammed Dogukan Aksu , Fatma Visal Okur , Tekin Aksu , Mehmet Ceyhan , Ates Kara , Ali Bulent Cengiz , Yasemin Ozsurekci , Sule Unal

Infectious complications remain the major cause of treatment-related morbidity and mortality in pediatric patients with acute lymphoblastic leukemia (ALL). This study retrospectively compared the patterns of infection in children treated with either the modified St. Jude Total XV protocol (n = 181) or the ALL-IC BFM 2009 protocol (n = 61) at a single center. Although the overall number of infection episodes was similar between the two groups, their distributions across treatment phases differed markedly. The ALL-IC BFM 2009 protocol was associated with a significantly greater incidence of infections during the induction phase, particularly in high-risk patients, who often presented with skin and gastrointestinal tract infections. In contrast, modified St. Jude Total XV protocol presented a greater infection risk during the re-induction phase. Gram-positive bacteria, especially Staphylococcus epidermidis, were the most frequently isolated pathogens in both cohorts, although the BFM group exhibited a higher proportion of gram-negative infections. The rates of documented viral infections in BFM cohort and modified St. Jude Total XV cohort were 21.4 % vs 9.2 %, respectively. Invasive fungal infection rate was found as 6.7 % in the modified St. Jude group and 4.0 % in the BFM group is in line with the literature. Multivariate analysis confirmed that severe neutropenia and the presence of a central venous catheter were strong independent predictors of infection frequency. These findings underscore protocol-specific differences in infectious risk profiles and emphasize the importance of tailored supportive care strategies in the management of pediatric ALL.

感染性并发症仍然是急性淋巴细胞白血病（ALL）患儿治疗相关发病率和死亡率的主要原因。本研究回顾性比较了在单个中心接受改良St. Jude Total XV方案（n = 181）或ALL-IC BFM 2009方案（n = 61）治疗的儿童感染模式。尽管两组之间感染事件的总次数相似，但它们在治疗阶段的分布明显不同。ALL-IC BFM 2009方案与诱导期感染发生率显著增加相关，特别是在经常出现皮肤和胃肠道感染的高危患者中。相比之下，改良的St. Jude Total XV方案在再诱导阶段的感染风险更大。革兰氏阳性细菌，尤其是表皮葡萄球菌，是两个队列中最常见的分离病原体，尽管BFM组表现出更高比例的革兰氏阴性感染。BFM队列和改良St. Jude Total XV队列中记录的病毒感染率分别为21.4% %和9.2% %。改良St. Jude组侵袭性真菌感染率为6.7 %，BFM组为4.0 %，与文献一致。多因素分析证实，严重中性粒细胞减少和中心静脉导管的存在是感染频率的强大独立预测因素。这些发现强调了不同方案在感染风险概况方面的差异，并强调了在儿科ALL治疗中定制支持性护理策略的重要性。

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引用次数: 0

Applicability of current prognostication models for MDS patients with DDX41 mutation 当前DDX41突变MDS患者预后模型的适用性

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-06 DOI: 10.1016/j.leukres.2025.108118

Nadia Toumeh, Yazan Jabban, Rong He, David Viswanatha, Dragan Jevremovic, Patricia T. Greipp, James M. Foran, Talha Badar, Cecilia Y. Arana Yi, Yael Kusne, Antoine N. Saliba, Mehrdad Hefazi Thorghabeh, Aasiya Matin, William J. Hogan, Mithun V. Shah, Abhishek A. Mangaonkar, Mrinal M. Patnaik, Hassan B. Alkhateeb, Aref Al-Kali

引用次数: 0

Low serum complement C3 levels are associated with adverse clinical outcomes in myelodysplastic syndromes 低血清补体C3水平与骨髓增生异常综合征的不良临床结果相关

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-10-03 DOI: 10.1016/j.leukres.2025.108116

Duobing Zou , Huanhuan Ying , Liang Yong , Jie Cao , Yanqing Liu , Guifang Ouyang , Qitian Mu

Background

Complement C3, a critical component of the complement system, has been implicated in cancer risk across various malignancies. However, its role in myelodysplastic syndromes (MDS) remains inadequately explored. This study investigates the impact of serum complement C3 levels on survival outcomes in patients with MDS.

Methods

Clinical data, including demographic characteristics (sex and age), hematological indices (white blood cell count and platelet count), bone marrow blast percentage, immunoglobulin levels (IgG, IgM, and IgA), and complement components (C3, C4, and Factor B), were retrospectively analyzed in 145 patients with MDS. Serum C3 levels were compared quantitatively between healthy controls and patients with MDS. Univariate and multivariate Cox proportional hazards regression analyses were employed to identify prognostic factors associated with clinical outcomes in MDS.

Results

A significant reduction in peripheral blood complement C3 levels was observed in patients with MDS compared to healthy controls (P < 0.0001). Patients with lower serum C3 levels exhibited notably poorer clinical outcomes, including reduced overall survival (OS; P = 0.019) and leukemia-free survival (LFS; P = 0.043). Multivariate Cox regression analysis, incorporating the Revised International Prognostic Scoring System (IPSS-R) but not the Molecular IPSS (IPSS-M), identified serum C3 levels below 79 mg/dL as an independent prognostic factor for both OS (P = 0.041) and LFS (P = 0.005).

Conclusion

Decreased serum complement C3 levels emerge as an independent prognostic biomarker in MDS, correlating with unfavorable clinical outcomes regardless of IPSS-R stratification. This novel parameter offers additional prognostic value and may enhance existing risk assessment tools in the clinical management of MDS.

补体C3是补体系统的一个重要组成部分，与各种恶性肿瘤的癌症风险有关。然而，其在骨髓增生异常综合征（MDS）中的作用仍未得到充分探讨。本研究探讨血清补体C3水平对MDS患者生存结局的影响。方法回顾性分析145例MDS患者的临床资料，包括人口统计学特征（性别、年龄）、血液学指标（白细胞计数、血小板计数）、骨髓原细胞百分比、免疫球蛋白水平（IgG、IgM、IgA）和补体成分（C3、C4、因子B）。定量比较健康对照组和MDS患者血清C3水平。采用单因素和多因素Cox比例风险回归分析来确定与MDS临床结果相关的预后因素。结果与健康对照组相比，MDS患者外周血补体C3水平显著降低（P <； 0.0001）。血清C3水平较低的患者表现出明显较差的临床结果，包括总生存期（OS; P = 0.019）和无白血病生存期（LFS; P = 0.043）降低。纳入修订国际预后评分系统（IPSS- r）而非分子IPSS （IPSS- m）的多变量Cox回归分析发现，血清C3水平低于79 mg/dL是OS （P = 0.041）和LFS （P = 0.005）的独立预后因素。结论血清补体C3水平降低是MDS的独立预后生物标志物，与IPSS-R分层无关，与不利的临床结果相关。这一新参数提供了额外的预后价值，并可能增强MDS临床管理中现有的风险评估工具。

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引用次数: 0

Multicenter retrospective analysis of the short-term efficacy and safety of the VAH regimen in the treatment of acute myeloid leukemia 多中心回顾性分析VAH方案治疗急性髓性白血病的短期疗效和安全性。

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-09-30 DOI: 10.1016/j.leukres.2025.108114

Ruihua Mi , Lin Chen , Lin Wang , Haiping Yang , Hongmian Zhao , Sun Wu , Yixuan Ma , Jia Liu , Xudong Wei

Objective

To retrospectively investigate the short-term efficacy and safety of the triple-drug combination regimen of venetoclax + azacitidine + homoharringtonine (VAH regimen) in patients with acute myeloid leukemia (AML).

Methods

Retrospective analysis was conducted on a total of 45 patients with newly diagnosed or refractory/relapsed AML, who were admitted to the Affiliated Cancer Hospital of Zhengzhou University, the First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, the Huaihe Hospital of Henan University, and The First Affiliated Hospital of Xinxiang Medical University from July 2022 to October 2024 and treated with the VAH regimen. The overall response rate and safety of this regimen were analyzed, and the relevant literature was reviewed.

Results

In the 23 newly treated patients, the overall response rate (ORR) (CR+CRi) was 65.2 % on day 15 of the VAH regimen and 82.6 % on day 29 after the end of cycle 1. The median duration of grade 3–4 neutropenia was 12.6 days. In the 22 refractory/relapsed patients, the ORR (CR+CRi) was 68.2 % on day 15 of the VAH regimen and 86.4 % on day 29 after the end of cycle 1, and the median duration of neutropenia was 14.4 days. The most common adverse reactions were myelosuppression and infection, both of which were within controllable limits. There was no death due to adverse reactions during treatment.

Conclusion

The VAH regimen yields a high remission rate in newly diagnosed and refractory/relapsed AML patients. This retrospective study provides a novel treatment strategy for AML patients.

目的：回顾性探讨维尼托克拉克斯+ 阿扎胞苷+ 高杉碱三联用药方案（VAH方案）治疗急性髓性白血病（AML）的近期疗效和安全性。方法：回顾性分析2022年7月至2024年10月在郑州大学附属肿瘤医院、河南科技大学第一附属医院及临床医学院、河南大学淮河医院、新乡医科大学第一附属医院接受VAH方案治疗的45例新诊断或难治/复发AML患者。分析该方案的总有效率和安全性，并对相关文献进行复习。结果：在23例新治疗的患者中，VAH方案第15天总缓解率（CR+CRi）为65.2% %，第1周期结束后第29天为82.6 %。3-4级中性粒细胞减少的中位持续时间为12.6天。在22例难治/复发患者中，VAH方案第15天的ORR （CR+CRi）为68.2% %，第1周期结束后第29天的ORR （CR+CRi）为86.4 %，中性粒细胞减少的中位持续时间为14.4天。最常见的不良反应是骨髓抑制和感染，均在可控范围内。治疗期间无不良反应死亡病例。结论：VAH方案对新诊断和难治性/复发AML患者有很高的缓解率。本回顾性研究为AML患者提供了一种新的治疗策略。

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引用次数: 0

Evaluating complete response/remission rate as a surrogate endpoint in relapsed/refractory chronic lymphocytic leukemia 评估完全缓解/缓解率作为复发/难治性慢性淋巴细胞白血病的替代终点

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-09-27 DOI: 10.1016/j.leukres.2025.108113

Lin Wang , Murat Kurt , Tim Disher , Fei Fei Liu , Samantha Craigie , Serena K. Perna , Elise Aronitz , Toby A. Eyre , Loic Ysebaert , Matthew S. Davids

Achieving complete response/remission (CR) by International Workshop on Chronic Lymphocytic Leukemia 2018 criteria indicates complete remission of leukemia in all disease compartments. We evaluated CR rate as a surrogate endpoint for progression-free survival (PFS) in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) using data from randomized controlled trials (RCT). A systematic literature review was conducted to identify RCTs with ≥ 2 treatment arms, parallel group design, and reporting CR rate and PFS in patients with R/R CLL/SLL. Association between treatment effects on CR rate and corresponding PFS changes contrasting treatment and control arms was estimated using a weighted linear model, Daniels and Hughes model, and Riley bivariate random-effects meta-analysis. Association between absolute CR rate and PFS within individual treatment arms was estimated using nonparametric (Cox) and parametric (exponential, Weibull, Gompertz) proportional hazards models. Twenty RCTs were identified including 5765 patients with R/R CLL/SLL investigating various treatments (Bruton tyrosine kinase inhibitors, a B-cell lymphoma 2 inhibitor, phosphatidylinositol 3-kinase inhibitors, chimeric antigen receptor T-cell therapy, anti-CD20 monoclonal antibody, chemotherapy). Across RCTs, higher odds of CR resulted in statistically significant lower hazards of disease progression/death, where each 10 % increase in CR rate was associated with a 26 % (95 % confidence interval, 22 %30 %) reduction in risk of progression/death. Cross-validation analyses demonstrated that treatment effects on CR rate reasonably predicted PFS benefits. Results were broadly consistent across different models. This study supports CR rate as an essential treatment goal and a valid surrogate endpoint in R/R CLL/SLL.

达到国际慢性淋巴细胞白血病研讨会2018标准的完全缓解/缓解（CR）表明所有疾病区室的白血病完全缓解。我们使用随机对照试验（RCT）的数据评估了CR率作为复发/难治性（R/R）慢性淋巴细胞白血病(CLL)/小淋巴细胞淋巴瘤（SLL）患者无进展生存（PFS）的替代终点。通过系统的文献综述，确定≥ 2个治疗组、平行组设计、报告R/R CLL/SLL患者的CR率和PFS的rct。采用加权线性模型、Daniels和Hughes模型和Riley双变量随机效应荟萃分析，估计治疗效果对CR率和相应PFS变化的相关性。使用非参数（Cox）和参数（指数、Weibull、Gompertz）比例风险模型估计各个治疗组中绝对CR率和PFS之间的关联。共纳入20项随机对照试验，包括5765例R/R CLL/SLL患者，研究了各种治疗方法（布鲁顿酪氨酸激酶抑制剂、b细胞淋巴瘤2抑制剂、磷脂酰肌醇3激酶抑制剂、嵌合抗原受体t细胞治疗、抗cd20单克隆抗体、化疗）。在所有随机对照试验中，较高的CR几率导致疾病进展/死亡风险的统计学显著降低，其中CR率每增加10 %，进展/死亡风险降低26 %（95 %可信区间，22 %30 %）。交叉验证分析表明，治疗对CR率的影响合理地预测了PFS的益处。不同模型的结果大致一致。本研究支持CR率作为R/R CLL/SLL的基本治疗目标和有效替代终点。

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引用次数: 0

Genes with altered expression by 5-Aza treatment in myeloid leukemia cells through methylation in intron 1 5-Aza处理通过内含子1甲基化改变髓系白血病细胞表达的基因

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-09-23 DOI: 10.1016/j.leukres.2025.108112

Machiko Fujioka , Hiroyuki Mishima , Hidehiro Itonaga , Yo Hamaguchi , Uladzislau Korzun , Koji Ando , Akira Kinoshita , Yasushi Miyazaki , Koh-ichiro Yoshiura

5-Azacitidine (5-Aza) is a hypomethylating agent with demonstrated therapeutic efficacy for myeloid leukemia. The aim of this study was to identify the genes that mediate the cell killing effect of 5-Aza against leukemia cells through their expression changes and DNA demethylation. RNA sequencing revealed 54 genes with increased transcription levels in both SKM-1 and KG-1a myeloid leukemia cell lines treated with 5-Aza. Long read sequencing revealed 79 genes in which intron 1 exhibited significant DNA demethylation after 5-Aza treatment. Forty-three genes showed both increased gene expression and DNA demethylation in intron 1 in cells treated with 5-Aza. Enrichment signaling pathway analysis demonstrated that genes were associated with “amino acid metabolism,” “neutrophil degranulation,” and “DNA damage response”. We evaluated the prognostic impacts of the 43 genes in acute myeloid leukemia patients using TCGA database. The results revealed that two genes (HDC and MICALL2) with increased expression in leukemia cells after 5-Aza treatment were associated with better overall survival, while six genes (BTG2, CD52, PECAM1, PIK3IP1, PTGS2, and TREML2) correlated with worse overall survival. This study revealed that the epigenetic regulation by DNA demethylation in intron 1 has an important role of 5-Aza treatment in myeloid leukemia cells, and suggests novel targets for the development of combination therapy with 5-Aza.

5-氮杂胞苷（5-Aza）是一种低甲基化药物，具有治疗髓性白血病的疗效。本研究的目的是通过5-Aza表达变化和DNA去甲基化来确定介导5-Aza对白血病细胞杀伤作用的基因。RNA测序显示，在5-Aza处理的SKM-1和KG-1a髓系白血病细胞株中，54个基因的转录水平升高。长读测序显示，在5-Aza处理后，79个基因的内含子1出现了显著的DNA去甲基化。在5-Aza处理的细胞中，43个基因在内含子1上的基因表达和DNA去甲基化都增加。富集信号通路分析表明，基因与“氨基酸代谢”、“中性粒细胞脱粒”和“DNA损伤反应”相关。我们使用TCGA数据库评估43个基因对急性髓系白血病患者预后的影响。结果显示，5-Aza治疗后，2个基因（HDC和MICALL2）在白血病细胞中表达增加与更好的总生存相关，而6个基因（BTG2、CD52、PECAM1、PIK3IP1、PTGS2和TREML2）与更差的总生存相关。本研究揭示了内含子1 DNA去甲基化的表观遗传调控在5-Aza治疗髓系白血病细胞中具有重要作用，并为开发5-Aza联合治疗提供了新的靶点。

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引用次数: 0

Low-dose ropeginterferon alfa-2b and peginterferon alfa-2a have comparable efficacy and tolerability in polycythemia vera 低剂量聚乙二醇干扰素α α -2b和聚乙二醇干扰素α α -2a治疗真性红细胞增多症的疗效和耐受性相当

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-09-19 DOI: 10.1016/j.leukres.2025.108110

Neville Lee Jr, Katie Erdos, Aqib Abdul Rahman, Richard T. Silver, Joseph M. Scandura, Ghaith Abu-Zeinah

引用次数: 0

Health system costs and autologous stem cell transplant receipt for participants with multiple myeloma in the Australian 45 and Up Study 澳大利亚45岁及以上研究中多发性骨髓瘤参与者的医疗系统费用和自体干细胞移植收据。

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-09-16 DOI: 10.1016/j.leukres.2025.108100

Sarsha Yap , Anna Kelly , David Goldsbury , Marianne F. Weber , Xue Qin Yu , Qingwei Luo , Karen Canfell , Eleonora Feletto

Background

In Australia, the number of people living with multiple myeloma (MM) is projected to increase. We examined the health system costs and autologous stem cell transplant (ASCT) receipt among participants with MM diagnosed between 2006 and 2019 from the Australian 45 and Up Study cohort (267,357 participants).

Materials and methods

We identified 520 participants diagnosed with MM using cancer registry records. Direct excess health system costs were calculated by subtracting the mean values observed for 2533 matched participants without cancer from those observed for participants with MM. Costs were calculated from 2 years pre-diagnosis up to 5 years post-diagnosis, for different phases of care and at end of life. Participant characteristics associated with health system costs were analysed using gamma regression. Characteristics associated with ASCT receipt were analysed using competing risks regression.

Results

Mean excess health system cost per person was $8846 in the year pre-diagnosis and peaked at $66,249 in the year post-diagnosis. From 2- to 5-years post-diagnosis, mean excess costs per person ranged between $36,453 and $43,059 and remained substantially higher than pre-diagnosis levels. Within the 5-years post-diagnosis, 125 (24.0 %) received ASCT. Older age at diagnosis was strongly associated with lower costs (each one-year increase, relative rate (RR)= 0.97, 95 % CI:0.96–0.98 for initial phase of care costs) and a lower rate of ASCT (each one-year increase, sub-hazard ratio (SHR)= 0.85, 95 % CI:0.83–0.87).

Conclusions

Health system costs for individuals with MM were significantly higher post-diagnosis than pre-diagnosis and remained elevated for at least 5-years. This work provides insights for future healthcare requirements for MM.

背景：在澳大利亚，患有多发性骨髓瘤（MM）的人数预计会增加。我们检查了2006年至2019年澳大利亚45岁及以上研究队列（267,357名参与者）中诊断为MM的参与者的卫生系统成本和自体干细胞移植（ASCT）接收情况。材料和方法：我们使用癌症登记记录确定了520名被诊断为MM的参与者。直接超额卫生系统成本是通过减去2533名没有癌症的匹配参与者观察到的平均值来计算的，从诊断前2年到诊断后5年，计算不同护理阶段和生命结束时的成本。使用伽玛回归分析了与卫生系统成本相关的参与者特征。使用竞争风险回归分析与ASCT接收相关的特征。结果：诊断前一年人均超额卫生系统费用为8846美元，诊断后一年最高为66249美元。从诊断后2年到5年，平均每人额外费用在36,453美元到43,059美元之间，仍然大大高于诊断前的水平。诊断后5年内，125例（24.0 %）接受ASCT。诊断年龄越大与较低的费用（每一年增加，相对率(RR)= 0.97,95 % CI:0.96-0.98初始阶段护理费用）和较低的ASCT率（每一年增加，亚危险比(SHR)= 0.85,95 % CI:0.83-0.87）密切相关。结论：MM患者的医疗系统成本在诊断后明显高于诊断前，并且在至少5年内保持高水平。这项工作为MM的未来医疗保健需求提供了见解。

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引用次数: 0

Pathogenic mechanisms and targeted therapies for anemia in myelodysplastic syndromes 骨髓增生异常综合征贫血的致病机制和靶向治疗

IF 2.2 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2025-09-13 DOI: 10.1016/j.leukres.2025.108099

Doudou Chang , Linhua Yang , Ruijuan Zhang

Myelodysplastic Syndromes (MDS) are malignant neoplasms of the myeloid lineage originating from hematopoietic stem cells (HSCs), characterized by ineffective hematopoiesis, blood cell dysplasia, and a high risk of transformation to acute leukemia. Anemia affects up to 90 % of MDS patients, significantly increasing symptom burden, impacting quality of life, accelerating disease progression, and is associated with increased morbidity and mortality. The limited therapeutic landscape for addressing anemia in MDS presents a significant challenge in clinical management. This review explores the mechanisms of anemia in MDS（including low-risk MDS and high-risk MDS）, covering disturbances in hematopoiesis, telomere dynamics, inflammation, immune dysregulation, alterations in iron metabolism, and the role of the bone marrow microenvironment. We examine how these factors contribute to the complex pathophysiology of MDS-related anemia and discuss their implications for treatment strategies. Furthermore, we highlight recent advances in understanding the molecular basis of MDS, which have paved the way for novel therapeutic approaches. These include targeted therapies addressing specific genetic mutations, immunomodulatory agents, and innovative approaches to stimulate effective erythropoiesis. We also review emerging treatments such as Luspatercept, along with other novel agents targeting specific pathways, and ongoing clinical trials exploring combination therapies and personalized treatment strategies.

骨髓增生异常综合征（MDS）是一种起源于造血干细胞（hsc）的髓系恶性肿瘤，其特点是造血功能低下、血细胞发育不良、转化为急性白血病的风险高。贫血影响高达90% %的MDS患者，显著增加症状负担，影响生活质量，加速疾病进展，并与发病率和死亡率增加相关。解决MDS患者贫血的治疗前景有限，这对临床管理提出了重大挑战。本文综述了MDS（包括低危MDS和高危MDS）贫血的机制，包括造血功能紊乱、端粒动力学、炎症、免疫失调、铁代谢改变以及骨髓微环境的作用。我们研究了这些因素如何促成mds相关贫血的复杂病理生理，并讨论了它们对治疗策略的影响。此外，我们强调了最近在理解MDS分子基础方面的进展，这些进展为新的治疗方法铺平了道路。这些包括针对特定基因突变的靶向治疗、免疫调节剂和刺激有效红细胞生成的创新方法。我们还回顾了新兴的治疗方法，如Luspatercept，以及其他针对特定途径的新型药物，以及正在进行的探索联合治疗和个性化治疗策略的临床试验。

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引用次数: 0