Leukemia research最新文献_第3页

Virologic effect and hepatotoxicity of BCR::ABL1 tyrosine kinase inhibitors in cancer patients with chronic hepatitis C virus infection: A prospective study BCR::ABL1酪氨酸激酶抑制剂对慢性丙型肝炎病毒感染的癌症患者的病毒学效应和肝毒性：前瞻性研究。

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2024-10-03 DOI: 10.1016/j.leukres.2024.107597

Khalis Mustafayev, Eduardo Yepez Guevara, Courtney D. DiNardo, Elias Jabbour, Issa C. Ghayas, Ravin Ratan, Naveen Pemmaraju, Harrys A. Torres

引用次数: 0

Therapeutic advances for the management of adult T cell leukemia: Where do we stand? 成人 T 细胞白血病的治疗进展：现状如何？

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2024-10-02 DOI: 10.1016/j.leukres.2024.107598

Hiba El Hajj , Olivier Hermine , Ali Bazarbachi

Adult T cell leukemia (ATL) is an aggressive blood malignancy secondary to chronic infection with the human T cell leukemia virus type I (HTLV-1) retrovirus. ATL encompasses four subtypes (acute, lymphoma, chronic, and smoldering), which exhibit different clinical characteristics and respond differently to various treatment strategies. Yet, all four subtypes are characterized by a dismal long-term prognosis and a low survival rate. While antiretroviral therapy improves overall survival outcomes in smoldering and chronic subtypes, survival remains poor in lymphoma subtypes despite their good response to intensive chemotherapy. Nonetheless, acute ATL remains the most aggressive form associated with profound immunosuppression, chemo-resistance and dismal prognosis. Targeted therapies such as monoclonal antibodies, epigenetic therapies, and arsenic/IFN, emerged as promising therapeutic approaches in ATL. Allogeneic hematopoietic cell transplantation is the only potentially curative modality, alas applicable to only a small percentage of patients. The recent findings demonstrating the expression of the viral oncoprotein Tax in primary ATL cells from patients with acute or chronic ATL, albeit at low levels, and their dependence on continuous Tax expression for their survival, position ATL as a virus-addicted leukemia and validates the rationale of anti-viral treatment strategies. This review provides a comprehensive overview on conventional, anti-viral and targeted therapies of ATL, with emphasis on Tax-targeted therapied in the pre-clinical and clinical settings.

成人 T 细胞白血病（ATL）是一种继发于人类 T 细胞白血病病毒 I 型（HTLV-1）逆转录病毒慢性感染的侵袭性血液恶性肿瘤。ATL 包括四种亚型（急性、淋巴瘤、慢性和烟雾型），它们表现出不同的临床特征，对各种治疗策略的反应也不尽相同。然而，这四种亚型的长期预后都很糟糕，存活率很低。抗逆转录病毒疗法可改善烟熏型和慢性亚型患者的总体存活率，而淋巴瘤亚型患者尽管对强化化疗反应良好，但存活率仍然很低。尽管如此，急性ATL仍然是最具侵袭性的淋巴瘤，具有严重的免疫抑制、化疗耐药和预后不良等特点。单克隆抗体、表观遗传疗法和砷/IFN等靶向疗法成为治疗ATL的有前途的方法。异基因造血细胞移植是唯一可能治愈的方法，但只适用于一小部分患者。最近的研究结果表明，急性或慢性 ATL 患者的原发性 ATL 细胞中存在病毒肿瘤蛋白 Tax 的表达（尽管水平较低），而且这些细胞的存活依赖于 Tax 的持续表达，这将 ATL 定义为一种病毒上瘾的白血病，并验证了抗病毒治疗策略的合理性。本综述全面概述了 ATL 的常规、抗病毒和靶向疗法，重点是临床前和临床环境中的 Tax 靶向疗法。

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引用次数: 0

Chemotherapy and allo-HSCT for young patients with aggressive ATL 对侵袭性ATL年轻患者进行化疗和异基因造血干细胞移植。

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2024-09-27 DOI: 10.1016/j.leukres.2024.107596

Shigeo Fuji

Adult T-cell leukemia-lymphoma (ATL) is an aggressive malignancy with a poor prognosis, especially for patients with the aggressive subtype. While conventional chemotherapy offers short-term disease control, allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most promising curative approach for young, transplant-eligible patients. This review focuses on current treatment strategies for aggressive ATL in this specific population. We discuss the rationale for early upfront allo-HSCT following induction chemotherapy. The advent of allo-HSCT using alternative donors, particularly haploidentical HCT, has broadened the applicability of early upfront allo-HSCT in patients with aggressive ATL worldwide. Finally, we address emerging therapies that may improve outcomes in the context of allo-HSCT, paving the way for further advancements in the treatment of aggressive ATL.

成人T细胞白血病淋巴瘤（ATL）是一种侵袭性恶性肿瘤，预后较差，尤其是侵袭性亚型患者。虽然传统化疗能在短期内控制病情，但对于符合移植条件的年轻患者来说，异基因造血干细胞移植（allo-HSCT）仍是最有希望治愈的方法。本综述将重点讨论目前针对这一特殊人群的侵袭性ATL的治疗策略。我们讨论了在诱导化疗后尽早进行前期allo-HSCT的理由。使用替代供者，尤其是单倍体同种异基因造血干细胞移植（HCT）的出现扩大了早期先期同种异基因造血干细胞移植在全球侵袭性 ATL 患者中的适用性。最后，我们探讨了可改善allo-HSCT治疗效果的新兴疗法，为进一步推动侵袭性ATL的治疗铺平了道路。

引用次数: 0

Clinical relevance of long non-coding RNA in acute myeloid leukemia: A systematic review with meta-analysis 长非编码 RNA 在急性髓性白血病中的临床意义：系统回顾与荟萃分析

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2024-09-23 DOI: 10.1016/j.leukres.2024.107595

Priya , Manoj Garg , Rashmi Talwar , Mohit Bharadwaj , Munindra Ruwali , Amit Kumar Pandey

Background

Long noncoding RNAs (lncRNAs) may function as prognostic biomarkers in acute myeloid leukaemia (AML). However, it is still unknown exactly how significant lncRNAs are for the prognosis of AML. With a focus on their prognostic and therapeutic potential, the study aimed to provide a comprehensive review of the literature regarding the role of lncRNAs in AML.

Method

Pub Med, The Cochrane Library, Embase, Science Direct, Web of science, Scopus, and Google scholar were searched until November, 2023. Original publications of any type exploring the prognostic and therapeutic potential of lncRNAs in AML patients were included. Heterogeneity and publication bias were examined using the I² test and a funnel plot, respectively. To quantify the relationship between various lncRNA expression in AML patient survival, odds ratios (ORs) or hazards ratios (HRs) with 95 % confidence intervals (CIs) were pooled. Quality of studies was assessed using the Critical Appraisal Checklists for Studies created by the Joanna Briggs Institute (JBI).

Results

Twenty-seven studies including 5665 subjects were selected for the final analysis. In patients with AML, abnormal lncRNA expression has been associated with significant worse overall survival (pooled HR = 2.05, 95 % CI = 1.79–2.30, P <0.001), shorter disease-free survival (pooled HR = 2.17, 95 % CI = 1.13–3.22, P< 0.001), and lower complete remission rate (pooled HR = 0.27, 95 % CI = 0.11–0.43, P< 0.001). Poor prognoses have been attributed to increased expression of HOX transcript antisense intergenic RNA (HOTAIR), Promoter Of CDKN1A Antisense DNA Damage Activated RNA (PANDAR), Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1), RP11–222K16.2, Taurine Upregulated Gene 1 (TUG1), Small Nucleolar RNA Host Gene 5 (SNHG5), Growth Arrest Specific 5 (GAS5), and H19 and decreased expression of IGF1R Antisense Imprinted Non-Protein Coding RNA (IRAIN).

Conclusion

The prognoses of AML patients are significantly associated with abnormally expressed lncRNAs, which may be used as prognostic indicators for predicting the patient outcomes.

背景长非编码RNA（lncRNA）可作为急性髓性白血病（AML）的预后生物标志物。然而，目前尚不清楚lncRNA对急性髓性白血病预后的确切意义。本研究以其预后和治疗潜力为重点，旨在对有关lncRNAs在AML中作用的文献进行全面综述。研究方法检索了Pub Med、The Cochrane Library、Embase、Science Direct、Web of science、Scopus和Google scholar，直至2023年11月。纳入了探讨 lncRNAs 在急性髓细胞性白血病患者中的预后和治疗潜力的任何类型的原始出版物。分别使用 I2 检验和漏斗图检验异质性和发表偏倚。为了量化各种lncRNA表达与AML患者生存之间的关系，对带有95%置信区间（CI）的几率比（OR）或危险比（HR）进行了汇总。研究质量采用乔安娜-布里格斯研究所（JBI）制定的 "研究关键评估清单"（Critical Appraisal Checklists for Studies）进行评估。在急性髓细胞性白血病患者中，lncRNA表达异常与较差的总生存期（汇总HR = 2.05，95 % CI = 1.79-2.30，P<0.001）、较短的无病生存期（汇总HR = 2.17，95 % CI = 1.13-3.22，P<0.001）和较低的完全缓解率（汇总HR = 0.27，95 % CI = 0.11-0.43，P<0.001）明显相关。预后不良的原因是 HOX 转录本反义基因间 RNA（HOTAIR）、Promoter Of CDKN1A Antisense DNA Damage Activated RNA（PANDAR）、Metastasis Associated Lung Adenocarcinoma Transcript 1（MALAT1）、RP11-222K16.2、牛磺酸上调基因1（TUG1）、小核极RNA宿主基因5（SNHG5）、生长停滞特异性5（GAS5）和H19的表达以及IGF1R反义印迹非蛋白编码RNA（IRAIN）的表达减少。

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引用次数: 0

Outcome of adolescents and young adult acute myeloid leukemia patients compared with middle-aged patients: A single centre retrospective experience 青少年和年轻成人急性髓性白血病患者与中年患者的预后比较：单一中心的回顾性经验。

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2024-09-21 DOI: 10.1016/j.leukres.2024.107586

RuiQi Chen, Mohaned AlHumaid, Georgina Daher-Reyes, Eshetu G. Atenafu, Steven Chan, Vikas Gupta, Dawn Maze, Andre C. Schuh, Mark D. Minden, Karen Yee, Aaron D. Schimmer, Hassan Sibai

Adult acute myeloid leukemia (AML) patients under the age of 60 often receive similar intensive treatments, while outcomes between the adolescent and young adult (AYA) age group (18−39) and middle-aged adults (40–60 years) were seldom reported. We aim to study the characteristics and outcomes of AYA patients in comparison to middle-aged adults. A retrospective analysis was performed on AYA patients treated at Princess Margaret Cancer Center between 2008 and 2018. The primary outcomes include overall survival (OS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM).

A total of 174 AYA patients and 176 middle-aged patients were included, with propensity score matching adjusting for potential major confounders. Comparing AYA and middle-aged patients, 5-year OS rates were similar at 54.6 % vs. 56.5 % (p=0.91), CIR rates at 29.5 % vs. 23.1 % (p=0.31), and similar NRM rates. Notably, non-transplanted AYA patients had a significantly higher CIR (39.8 %) compared to middle-aged patients (19.6 %) (p=0.0324), with more primary refractory/early relapsing disease. An observed trend toward improved OS in AYA patients post-2015 coincided with FLAG-IDA and haploidentical transplant implementations.

In conclusion, the study suggests that AYA patients, particularly those not undergoing transplantation, may benefit from more intensive treatment strategies, emphasizing the need for tailored approaches in this age group.

60 岁以下的成人急性髓性白血病（AML）患者通常会接受类似的强化治疗，而青少年和年轻成人（AYA）年龄组（18-39 岁）与中年成人（40-60 岁）之间的治疗效果却鲜有报道。我们旨在研究青少年和青年患者与中年人相比的特征和疗效。我们对 2008 年至 2018 年期间在玛格丽特公主癌症中心接受治疗的青壮年患者进行了回顾性分析。主要结果包括总生存期（OS）、累积复发率（CIR）和非复发死亡率（NRM）。共纳入174名青壮年患者和176名中年患者，并对潜在的主要混杂因素进行倾向评分匹配调整。对比青壮年患者和中年患者，5年OS率相似，分别为54.6%和56.5%（P=0.91），CIR率分别为29.5%和23.1%（P=0.31），NRM率相似。值得注意的是，与中年患者（19.6%）相比，未接受移植的青壮年患者的CIR（39.8%）明显更高（p=0.0324），原发性难治/早期复发的疾病也更多。2015年后，随着FLAG-IDA和单倍体移植的实施，观察到AYA患者的OS呈改善趋势。总之，该研究表明，AYA 患者，尤其是未接受移植的患者，可能会从更密集的治疗策略中获益，这也强调了在这一年龄组中采取针对性治疗方法的必要性。

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引用次数: 0

Assessing the risk of venous thromboembolism and bleeding among patients with myeloproliferative neoplasms undergoing total knee and hip arthroplasty 评估接受全膝关节和髋关节置换术的骨髓增生性肿瘤患者发生静脉血栓栓塞和出血的风险

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2024-09-21 DOI: 10.1016/j.leukres.2024.107591

Josue Marquez , Samantha Simon , Jeffrey I. Zwicker, Robert Flaumenhaft, Brian Hollenbeck, Rushad Patell

引用次数: 0

Patient-centric care in myelodysplastic syndromes: A global systematic literature review and gap analysis 骨髓增生异常综合征中以患者为中心的护理：全球系统性文献回顾与差距分析

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2024-09-21 DOI: 10.1016/j.leukres.2024.107592

Edward P. Armstrong , Duska M. Franic , Daniel C. Malone , Patrick Mellors , Sissi V. Pham , Cristina Masseria , Lorie Mody , Cosmina Hogea

Background

Disease progression and poor prognosis in higher-risk (HR) myelodysplastic syndrome (MDS) create an urgent need for interventions to improve the patient care experience in this vulnerable population. Patient-centric physician-supported strategies in conjunction with emerging therapies can help advance overall care and improve outcomes. The objective of this study was to evaluate patient-centric care (PCC) in the treatment of HR-MDS and identify opportunities to develop strategies to address care gaps for an optimal patient care experience.

Methods

A global systematic literature review (SLR) was conducted by cross-referencing MDS/HR-MDS with PCC terms, using PubMed, Embase, and Cochrane Collaboration databases (2017–2022) in accordance with Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines.

Results

In all, 59 MDS articles (45 empirical, 14 reviews) met the study inclusion criteria. Of these, 6 empirical articles focused on the HR-MDS population while none of the reviews did. Identified themes fell into 2 categories: health-related quality of life (HRQoL) and disparities. HRQoL was further categorized based on findings in the literature to include groupings of patient-reported outcomes (PROs), fatigue/frailty, and patient/preferences/treatment decisions/shared decision making (SDM).

Conclusions

With new treatments potentially on the horizon for HR-MDS, a call to action is timely to address the overall lack of empirical PCC data. The patient-centric approach presents critical opportunities for integration of physician-supported strategies with more effective first-line therapies to help optimize the journey of patients with HR-MDS and ensure meaningful outcomes by reducing patient/caregiver burden, aligning with and respecting patient preferences, and including patients as active participants in their treatment.

背景高危（HR）骨髓增生异常综合征（MDS）的疾病进展和不良预后导致迫切需要采取干预措施来改善这一脆弱人群的患者护理体验。以患者为中心的医生支持策略与新兴疗法相结合，有助于推进整体护理并改善预后。本研究的目的是评估在治疗 HR-MDS 过程中以患者为中心的护理（PCC），并确定制定策略的机会，以弥补护理差距，实现最佳的患者护理体验。方法根据系统性综述和荟萃分析首选报告项目（PRISMA）指南，使用 PubMed、Embase 和 Cochrane Collaboration 数据库（2017-2022 年），将 MDS/HR-MDS 与 PCC 术语交叉引用，进行了全球系统性文献综述（SLR）。其中，6 篇经验性文章侧重于 HR-MDS 群体，而没有一篇综述文章侧重于 HR-MDS 群体。确定的主题分为两类：与健康相关的生活质量（HRQoL）和差异。根据文献中的发现，对 HRQoL 进行了进一步分类，包括患者报告结果 (PRO)、疲劳/虚弱以及患者/偏好/治疗决定/共同决策 (SDM) 等分组。以患者为中心的方法提供了将医生支持的策略与更有效的一线疗法相结合的重要机会，有助于优化 HR-MDS 患者的治疗过程，并通过减轻患者/护理人员的负担、符合并尊重患者的偏好以及让患者积极参与治疗，确保获得有意义的治疗结果。

{"title":"Patient-centric care in myelodysplastic syndromes: A global systematic literature review and gap analysis","authors":"Edward P. Armstrong , Duska M. Franic , Daniel C. Malone , Patrick Mellors , Sissi V. Pham , Cristina Masseria , Lorie Mody , Cosmina Hogea","doi":"10.1016/j.leukres.2024.107592","DOIUrl":"10.1016/j.leukres.2024.107592","url":null,"abstract":"<div><h3>Background</h3><div>Disease progression and poor prognosis in higher-risk (HR) myelodysplastic syndrome (MDS) create an urgent need for interventions to improve the patient care experience in this vulnerable population. Patient-centric physician-supported strategies in conjunction with emerging therapies can help advance overall care and improve outcomes. The objective of this study was to evaluate patient-centric care (PCC) in the treatment of HR-MDS and identify opportunities to develop strategies to address care gaps for an optimal patient care experience.</div></div><div><h3>Methods</h3><div>A global systematic literature review (SLR) was conducted by cross-referencing MDS/HR-MDS with PCC terms, using PubMed, Embase, and Cochrane Collaboration databases (2017–2022) in accordance with Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines.</div></div><div><h3>Results</h3><div>In all, 59 MDS articles (45 empirical, 14 reviews) met the study inclusion criteria. Of these, 6 empirical articles focused on the HR-MDS population while none of the reviews did. Identified themes fell into 2 categories: health-related quality of life (HRQoL) and disparities. HRQoL was further categorized based on findings in the literature to include groupings of patient-reported outcomes (PROs), fatigue/frailty, and patient/preferences/treatment decisions/shared decision making (SDM).</div></div><div><h3>Conclusions</h3><div>With new treatments potentially on the horizon for HR-MDS, a call to action is timely to address the overall lack of empirical PCC data. The patient-centric approach presents critical opportunities for integration of physician-supported strategies with more effective first-line therapies to help optimize the journey of patients with HR-MDS and ensure meaningful outcomes by reducing patient/caregiver burden, aligning with and respecting patient preferences, and including patients as active participants in their treatment.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"147 ","pages":"Article 107592"},"PeriodicalIF":2.1,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142327730","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

Development and validation of a predictive model for tumor lysis syndrome in childhood acute lymphoblastic leukemia 儿童急性淋巴细胞白血病肿瘤溶解综合征预测模型的开发与验证

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2024-09-19 DOI: 10.1016/j.leukres.2024.107587

Yao Xiao , Li Xiao , Ximing Xu , Xianmin Guan , Yuxia Guo , Yali Shen , XiaoYing Lei , Ying Dou , Jie Yu

Background

Tumor lysis syndrome (TLS) frequently manifests shortly after induction chemotherapy for acute lymphoblastic leukemia (ALL), with the potential for swift progression. This study endeavored to develop a nomogram to predict the risk of TLS, utilizing clinical indicators present at the time of ALL diagnosis.

Methods

We retrospectively gathered data from 2243 patients with ALL, spanning December 2008 to December 2021, utilizing the clinical research big data platform of the National Center for Clinical Research on Children's Health and Diseases. The Least Absolute Shrinkage and Selection Operator (LASSO) method was employed to filter variables and identify predictors, followed by the application of multivariate logistic regression to construct the nomogram.

Results

The LASSO regression identified six critical variables among ALL patients, upon which a nomogram was subsequently constructed. Multifactorial logistic regression revealed that an elevated white blood cell count (WBC), serum phosphorus <2.1 mmol/L, potassium <3.5 mmol/L, aspartate transaminase (AST) ≥50 U/L, uric acid (UA) ≥476μmol/L, and the presence of acute kidney injury (AKI) at the time of initial diagnosis were significant risk factors for the development of TLS in ALL patients (P<0.05). The predictive model achieved an area under the receiver operating characteristic curve (AUC) of 0.824 [95 % CI (0.783, 0.865)], with an internal validation AUC of 0.859 [95 % CI (0.806, 0.912)]. The Hosmer-Lemeshow goodness-of-fit test confirmed the model’s robustness (P=0.687 for the training cohort; P=0.888 for the validation cohort). Decision curve analysis (DCA) indicated that the predictive model provided substantial clinical benefit across threshold probabilities ranging from 10 % to 70 %.

Conclusions

A nomogram incorporating six predictive variables holds significant potential for accurately forecasting TLS in pediatric patients with ALL.

背景急性淋巴细胞白血病（ALL）诱导化疗后不久常出现肿瘤溶解综合征（TLS），并有可能迅速恶化。方法我们利用国家儿童健康与疾病临床研究中心的临床研究大数据平台，回顾性地收集了2243例ALL患者的数据，时间跨度为2008年12月至2021年12月。结果 LASSO回归在ALL患者中发现了6个关键变量，并据此构建了提名图。多因素逻辑回归显示，白细胞计数（WBC）升高、血清磷<2.1 mmol/L、钾<3.5 mmol/L、天门冬氨酸转氨酶（AST）≥50 U/L、尿酸（UA）≥476μmol/L以及初诊时存在急性肾损伤（AKI）是ALL患者发生TLS的显著风险因素（P<0.05）。预测模型的接收者操作特征曲线下面积（AUC）为 0.824 [95 % CI (0.783, 0.865)]，内部验证 AUC 为 0.859 [95 % CI (0.806, 0.912)]。Hosmer-Lemeshow 拟合优度检验证实了该模型的稳健性（训练队列的 P=0.687；验证队列的 P=0.888）。结论包含六个预测变量的提名图在准确预测小儿 ALL 患者的 TLS 方面具有巨大潜力。

{"title":"Development and validation of a predictive model for tumor lysis syndrome in childhood acute lymphoblastic leukemia","authors":"Yao Xiao , Li Xiao , Ximing Xu , Xianmin Guan , Yuxia Guo , Yali Shen , XiaoYing Lei , Ying Dou , Jie Yu","doi":"10.1016/j.leukres.2024.107587","DOIUrl":"10.1016/j.leukres.2024.107587","url":null,"abstract":"<div><h3>Background</h3><div>Tumor lysis syndrome (TLS) frequently manifests shortly after induction chemotherapy for acute lymphoblastic leukemia (ALL), with the potential for swift progression. This study endeavored to develop a nomogram to predict the risk of TLS, utilizing clinical indicators present at the time of ALL diagnosis.</div></div><div><h3>Methods</h3><div>We retrospectively gathered data from 2243 patients with ALL, spanning December 2008 to December 2021, utilizing the clinical research big data platform of the National Center for Clinical Research on Children's Health and Diseases. The Least Absolute Shrinkage and Selection Operator (LASSO) method was employed to filter variables and identify predictors, followed by the application of multivariate logistic regression to construct the nomogram.</div></div><div><h3>Results</h3><div>The LASSO regression identified six critical variables among ALL patients, upon which a nomogram was subsequently constructed. Multifactorial logistic regression revealed that an elevated white blood cell count (WBC), serum phosphorus <2.1 mmol/L, potassium <3.5 mmol/L, aspartate transaminase (AST) ≥50 U/L, uric acid (UA) ≥476μmol/L, and the presence of acute kidney injury (AKI) at the time of initial diagnosis were significant risk factors for the development of TLS in ALL patients (P<0.05). The predictive model achieved an area under the receiver operating characteristic curve (AUC) of 0.824 [95 % CI (0.783, 0.865)], with an internal validation AUC of 0.859 [95 % CI (0.806, 0.912)]. The Hosmer-Lemeshow goodness-of-fit test confirmed the model’s robustness (P=0.687 for the training cohort; P=0.888 for the validation cohort). Decision curve analysis (DCA) indicated that the predictive model provided substantial clinical benefit across threshold probabilities ranging from 10 % to 70 %.</div></div><div><h3>Conclusions</h3><div>A nomogram incorporating six predictive variables holds significant potential for accurately forecasting TLS in pediatric patients with ALL.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"146 ","pages":"Article 107587"},"PeriodicalIF":2.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142312642","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

Gene regulatory mechanisms of T cell exhaustion in diffuse large B cell lymphoma based on single-cell transcriptome data 基于单细胞转录组数据的弥漫大 B 细胞淋巴瘤 T 细胞衰竭的基因调控机制。

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2024-09-19 DOI: 10.1016/j.leukres.2024.107588

Zhencang Zhou , Pinwei Zhu , Jinli Ge, Qiang Li, Hang Li, Nana Zhe, Zhaoyu Liu, Dengke Chen

Diffuse large B cell lymphoma (DLBCL) is a heterogeneous and aggressive B cell malignancy that accounts for about 30 % of non-Hodgkin lymphomas. The current standard treatment for DLBCL is rituximab plus chemotherapy, but many patients are refractory or relapse, indicating the need for improved understanding of its molecular pathology. T cell exhaustion is a state of dysfunction or impairment that occurs in chronic infections or cancers, and is associated with poor prognosis in DLBCL. However, the molecular mechanisms of T cell exhaustion in DLBCL are poorly understood. In this study, we performed a comprehensive analysis of T cell exhaustion in DLBCL using public single-cell transcriptome data. We identified different subtypes of T cells and characterized their gene expression features. We found that DLBCL had a significantly higher proportion of exhausted T cells than normal tonsil, and that exhausted T cells had distinct gene expression signatures from non-exhausted T cells. These signatures included genes related to inhibitory receptors, cytokines, transcription factors and metabolic enzymes. We also found that ID3 gene was significantly upregulated in exhausted T cells in DLBCL, which may play a key role in T cell exhaustion. We constructed a protein-protein interaction network, identifying major hub proteins involved in T cell exhaustion or migration. We also performed KEGG and GO enrichment analysis for the differentially expressed genes between exhausted and non-exhausted T cells, and found important signaling pathways related to T cell exhaustion in DLBCL. Our results provide new insights into the molecular mechanisms underlying T cell exhaustion and offer novel therapeutic targets for this complex disease.

弥漫大 B 细胞淋巴瘤（DLBCL）是一种异质性侵袭性 B 细胞恶性肿瘤，约占非霍奇金淋巴瘤的 30%。目前治疗 DLBCL 的标准疗法是利妥昔单抗加化疗，但许多患者难治或复发，这表明需要进一步了解其分子病理学。T细胞衰竭是慢性感染或癌症中出现的一种功能障碍或损伤状态，与DLBCL的不良预后有关。然而，人们对DLBCL中T细胞衰竭的分子机制知之甚少。在本研究中，我们利用公开的单细胞转录组数据对 DLBCL 中的 T 细胞衰竭进行了全面分析。我们确定了不同亚型的 T 细胞，并描述了它们的基因表达特征。我们发现，DLBCL中衰竭T细胞的比例明显高于正常扁桃体，而且衰竭T细胞与非衰竭T细胞有不同的基因表达特征。这些特征包括与抑制受体、细胞因子、转录因子和代谢酶相关的基因。我们还发现，ID3基因在DLBCL衰竭T细胞中明显上调，这可能在T细胞衰竭中起到关键作用。我们构建了一个蛋白-蛋白相互作用网络，确定了参与T细胞衰竭或迁移的主要枢纽蛋白。我们还对衰竭T细胞和非衰竭T细胞的差异表达基因进行了KEGG和GO富集分析，发现了与DLBCL中T细胞衰竭相关的重要信号通路。我们的研究结果为T细胞衰竭的分子机制提供了新的见解，并为这种复杂疾病提供了新的治疗靶点。

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引用次数: 0

Strategies to overcome splicing variants interference in mutational testing for BCR::ABL1 KD 克服剪接变体干扰 BCR::ABL1 KD 突变检测的策略

IF 2.1 4区医学 Q3 HEMATOLOGY

Leukemia research

Pub Date : 2024-09-18 DOI: 10.1016/j.leukres.2024.107594

Juliana Bulchi, Leandro Farias, Daniel Blajberg Schaffel, Bruna Sabioni, Telma França Padilha, Marianne Camile Silva de Sousa, Gustavo Trevizani Stelzer, Ilana Zalcberg, Luciana Mayumi Gutiyama

引用次数: 0