Leukemia research最新文献

{"title":"A phase I study of the myeloid cell leukemia 1 (MCL1) inhibitor tapotoclax (AMG 176) in patients with myelodysplastic syndromes after hypomethylating agent failure","authors":"Kelly S. Chien, Juan Jose Rodriguez-Sevilla, Yesid Alvarado, Guillermo Montalban-Bravo, Danielle E. Hammond, Mahesh Swaminathan, Alexandre Bazinet, Jacqueline Kimberley, Kristy Bodden, Heather Schneider, Xiao Qin Dong, Sherry A. Pierce, Xuelin Huang, Elias J. Jabbour, Hagop M. Kantarjian, Guillermo Garcia-Manero","doi":"10.1016/j.leukres.2024.107602","DOIUrl":"10.1016/j.leukres.2024.107602","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"147 ","pages":"Article 107602"},"PeriodicalIF":2.1,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142503152","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}

{"title":"Virologic effect and hepatotoxicity of BCR::ABL1 tyrosine kinase inhibitors in cancer patients with chronic hepatitis C virus infection: A prospective study","authors":"Khalis Mustafayev, Eduardo Yepez Guevara, Courtney D. DiNardo, Elias Jabbour, Issa C. Ghayas, Ravin Ratan, Naveen Pemmaraju, Harrys A. Torres","doi":"10.1016/j.leukres.2024.107597","DOIUrl":"10.1016/j.leukres.2024.107597","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"147 ","pages":"Article 107597"},"PeriodicalIF":2.1,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378003","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}

{"title":"Therapeutic advances for the management of adult T cell leukemia: Where do we stand?","authors":"Hiba El Hajj ,&nbsp;Olivier Hermine ,&nbsp;Ali Bazarbachi","doi":"10.1016/j.leukres.2024.107598","DOIUrl":"10.1016/j.leukres.2024.107598","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"147 ","pages":"Article 107598"},"PeriodicalIF":2.1,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375649","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}

{"title":"Chemotherapy and allo-HSCT for young patients with aggressive ATL","authors":"Shigeo Fuji","doi":"10.1016/j.leukres.2024.107596","DOIUrl":"10.1016/j.leukres.2024.107596","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"147 ","pages":"Article 107596"},"PeriodicalIF":2.1,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142375648","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}

{"title":"Clinical relevance of long non-coding RNA in acute myeloid leukemia: A systematic review with meta-analysis","authors":"Priya ,&nbsp;Manoj Garg ,&nbsp;Rashmi Talwar ,&nbsp;Mohit Bharadwaj ,&nbsp;Munindra Ruwali ,&nbsp;Amit Kumar Pandey","doi":"10.1016/j.leukres.2024.107595","DOIUrl":"10.1016/j.leukres.2024.107595","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Method</h3><div>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).</div></div><div><h3>Results</h3><div>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 &lt;0.001), shorter disease-free survival (pooled HR = 2.17, 95 % CI = 1.13–3.22, P&lt; 0.001), and lower complete remission rate (pooled HR = 0.27, 95 % CI = 0.11–0.43, P&lt; 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).</div></div><div><h3>Conclusion</h3><div>The prognoses of AML patients are significantly associated with abnormally expressed lncRNAs, which may be used as prognostic indicators for predicting the patient outcomes.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"147 ","pages":"Article 107595"},"PeriodicalIF":2.1,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142323970","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}

{"title":"Outcome of adolescents and young adult acute myeloid leukemia patients compared with middle-aged patients: A single centre retrospective experience","authors":"RuiQi Chen,&nbsp;Mohaned AlHumaid,&nbsp;Georgina Daher-Reyes,&nbsp;Eshetu G. Atenafu,&nbsp;Steven Chan,&nbsp;Vikas Gupta,&nbsp;Dawn Maze,&nbsp;Andre C. Schuh,&nbsp;Mark D. Minden,&nbsp;Karen Yee,&nbsp;Aaron D. Schimmer,&nbsp;Hassan Sibai","doi":"10.1016/j.leukres.2024.107586","DOIUrl":"10.1016/j.leukres.2024.107586","url":null,"abstract":"<div><div>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).</div><div>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.</div><div>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.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"147 ","pages":"Article 107586"},"PeriodicalIF":2.1,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142365754","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}

{"title":"Assessing the risk of venous thromboembolism and bleeding among patients with myeloproliferative neoplasms undergoing total knee and hip arthroplasty","authors":"Josue Marquez ,&nbsp;Samantha Simon ,&nbsp;Jeffrey I. Zwicker,&nbsp;Robert Flaumenhaft,&nbsp;Brian Hollenbeck,&nbsp;Rushad Patell","doi":"10.1016/j.leukres.2024.107591","DOIUrl":"10.1016/j.leukres.2024.107591","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"146 ","pages":"Article 107591"},"PeriodicalIF":2.1,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322721","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}

{"title":"Patient-centric care in myelodysplastic syndromes: A global systematic literature review and gap analysis","authors":"Edward P. Armstrong ,&nbsp;Duska M. Franic ,&nbsp;Daniel C. Malone ,&nbsp;Patrick Mellors ,&nbsp;Sissi V. Pham ,&nbsp;Cristina Masseria ,&nbsp;Lorie Mody ,&nbsp;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}

{"title":"Development and validation of a predictive model for tumor lysis syndrome in childhood acute lymphoblastic leukemia","authors":"Yao Xiao ,&nbsp;Li Xiao ,&nbsp;Ximing Xu ,&nbsp;Xianmin Guan ,&nbsp;Yuxia Guo ,&nbsp;Yali Shen ,&nbsp;XiaoYing Lei ,&nbsp;Ying Dou ,&nbsp;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 &lt;2.1 mmol/L, potassium &lt;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&lt;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}

{"title":"Gene regulatory mechanisms of T cell exhaustion in diffuse large B cell lymphoma based on single-cell transcriptome data","authors":"Zhencang Zhou ,&nbsp;Pinwei Zhu ,&nbsp;Jinli Ge,&nbsp;Qiang Li,&nbsp;Hang Li,&nbsp;Nana Zhe,&nbsp;Zhaoyu Liu,&nbsp;Dengke Chen","doi":"10.1016/j.leukres.2024.107588","DOIUrl":"10.1016/j.leukres.2024.107588","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"146 ","pages":"Article 107588"},"PeriodicalIF":2.1,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142290398","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}