Leukemia research最新文献

{"title":"The relationship between clinical prognostic factors, microvascular density, and tumor-infiltrating lymphocytes with CD47 and SIRPα expression in diffuse large B cell lymphomas","authors":"Aydan Kılıçarslan ,&nbsp;Sevdenur Özdüzgün Polat ,&nbsp;Hayriye Tatlı Doğan ,&nbsp;Tuğba Dilay Kökenek Ünal ,&nbsp;Şefika Karabulut ,&nbsp;Gülsüm Özet","doi":"10.1016/j.leukres.2024.107636","DOIUrl":"10.1016/j.leukres.2024.107636","url":null,"abstract":"<div><div>CD47 interacts with signal regulatory protein alpha (SIRPα) on macrophages to deliver an anti-phagocytic signal, enabling tumor cells to evade immune destruction. This study explores the relationship between CD47 and SIRPα expression and key clinical prognostic factors, microvascular density (MVD), and tumor-infiltrating lymphocytes (TIL) in Diffuse Large B Cell Lymphoma (DLBCL) cases. We analyzed tissue samples from 122 DLBCL cases using tissue microarray (TMA) blocks and immunohistochemical staining for CD47, SIRPα, CD31, and CD3. CD47 expression was scored using the Allred scoring system, and SIRPα expression was quantified based on the percentage of positive membranous and cytoplasmic expression. Clinical data, including IPI scores, relapse rates, and gene expression profiles, were correlated with the immunohistochemical findings.CD47 expression score ≥ 6 was significantly associated with the DLBCL-ABC phenotype (p = 0.029), higher IPI scores (p = 0.020), and increased relapse rates (p = 0.021). High SIRPα expression (≥25 % staining) was also linked to the ABC phenotype (p = 0.022) and frequent relapses (p = 0.021). Notably, cases with high microvascular density exhibited lower SIRPα expression (p = 0.013). There was no significant relationship between MVD and CD47 or other clinical prognostic factors. Additionally, higher CD3-positive TIL percentages were inversely correlated with IPI scores (p = 0.005), although no significant association was found between CD3 and CD47-SIRPα. The study reveals that increased CD47-SIRPα expression is partially linked to adverse prognostic indicators and reduced MVD in DLBCL cases. These findings suggest that targeting the CD47-SIRPα axis could offer a novel therapeutic approach in DLBCL, particularly for patients with poor prognostic features.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"149 ","pages":"Article 107636"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895853","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":"Exploring the significance of MDM2 gene promoter variants in chronic myeloid leukemia","authors":"María Belén Fontecha ,&nbsp;María del Rosario Anadón ,&nbsp;Inés María Martínez Lahitou ,&nbsp;Natalia Weich ,&nbsp;Raquel Bengió ,&nbsp;Beatriz Moiraghi ,&nbsp;Irene Larripa ,&nbsp;Ariela Freya Fundia","doi":"10.1016/j.leukres.2025.107644","DOIUrl":"10.1016/j.leukres.2025.107644","url":null,"abstract":"<div><div>Tyrosine kinase inhibitors (TKIs) targeting <em>BCR::ABL1</em> are highly successful in chronic myeloid leukemia (CML). However, extensive interpatient variability in therapeutic responses and resistance supports the need to find new prognostic biomarkers. We have previously reported that <em>TP53</em> SNP215 variant affects CML risk and clinical outcome. We aimed to evaluate the role of <em>MDM2</em> genetic variants in CML susceptibility and treatment response to TKIs. We genotyped five <em>MDM2</em> promoter variants (del1518, SNP309, SNP285, SNP288 and SNP344) in 135 CML patients and 136 healthy individuals. Our study showed that <em>MDM2</em> variants alone or in combination had no effect on CML susceptibility. The analysis of <em>MDM2</em> genotypes in relation to patients’ clinical parameters revealed that individuals with SNP309 G/G genotypes were at a significantly increased risk of undergoing molecular response failure (p = 0.044). Improved overall survival was also observed for non-responders with the alternative <em>MDM2</em> del1518 del allele (p = 0.017) as well as for <em>MDM2</em> del1518-SNP309 combinations with alternative genotypes (p = 0.014). In addition, combinatorial analysis demonstrated that alternative <em>MDM2</em> SNP309 and <em>TP53</em> SNP215 genotypes together are associated with faster achievement of MR² (p = 0.029) and MMR (p = 0.042) in non-responders, suggesting a relationship with a favorable outcome. Overall, our study highlights the influence of <em>MDM2</em> variants on clinical outcome, supporting that specific genotypes, alone or in combination, underlie the treatment-responsive phenotype.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"149 ","pages":"Article 107644"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007865","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":"New treatments for adult T-cell leukemia/lymphoma","authors":"Zachary D. Epstein-Peterson ,&nbsp;Ashwath Gurumurthi ,&nbsp;Steven M. Horwitz","doi":"10.1016/j.leukres.2025.107642","DOIUrl":"10.1016/j.leukres.2025.107642","url":null,"abstract":"<div><div>Adult T cell leukemia lymphoma (ATL) is a mature T cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1). ATL is endemic in specific geographic regions of the world closely related to areas with high prevalence of HLTV-1 infection, including Southwestern Japan, the Caribbean Basin, Central Africa, South America, Northern and Central Australia. HLTV-1 is primarily transmitted through breastmilk in asymptomatic carriers with a long latency period before transformation into ATL in 3 – 5 % of carriers after acquisition of multiple leukemogenic mutations. The Shimoyama classification established by the Japanese Lymphoma Study Group more than three decades ago remains clinically relevant and practical for guiding treatment. Due to the rarity of this illness, prospective, large prospective clinical are challenging to perform and treatment recommendations are based upon limited evidence. Aggressive disease subtypes have median survival ranging in months and the only curative therapy remains achieving deep remission with induction therapy followed by consolidative allogeneic transplantation. The prognosis for relapsed disease remains dismal due to chemo-refractoriness and limited therapeutic options. Herein, we review the current landscape of novel therapeutic agents with a focus on relapsed and refractory ATL including their mechanisms of action, resistance, and clinical efficacy.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"149 ","pages":"Article 107642"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029134","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":"A novel KMT2A::DCP1A fusion gene in acute myeloid leukemia","authors":"Ailing Deng ,&nbsp;Fenghong Zhang ,&nbsp;Man Wang,&nbsp;Dongyun Jiang,&nbsp;Jiannong Cen,&nbsp;Mengxing Xue,&nbsp;Yun Wang,&nbsp;Xueqing Dou,&nbsp;Qian Wu,&nbsp;Xiaofei Yang,&nbsp;Suning Chen","doi":"10.1016/j.leukres.2025.107645","DOIUrl":"10.1016/j.leukres.2025.107645","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"149 ","pages":"Article 107645"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007846","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":"Targeted antibody therapy as a treatment strategy for aggressive adult T-cell leukemia/lymphoma","authors":"Makoto Yoshimitsu","doi":"10.1016/j.leukres.2025.107653","DOIUrl":"10.1016/j.leukres.2025.107653","url":null,"abstract":"<div><div>The standard treatment for aggressive adult T-cell leukemia/lymphoma (ATL) is multi-agent chemotherapy, but the use of more intense cytotoxic anticancer agents is becoming more difficult with the aging of patients at the time of diagnosis. As a means of overcoming this hurdle, antibody drugs, which are supposed to be less toxic, have been developed for ATL. The advent of the anti-CC chemokine receptor 4 (CCR4) antibody mogamulizumab has significantly advanced ATL treatment. Real-world data and a phase 2 clinical trial suggest the efficacy and manageable safety profile of mogamulizumab with combination chemotherapy in elderly patients. Interestingly, mogamulizumab has performed well in cases with CCR4 mutations and cutaneous adverse events. In addition, emerging immunotherapies, including Tax peptide dendritic cell vaccines, immune checkpoint inhibitors, and Chimeric Antigen Receptor-T cell therapy, are under investigation. These innovative approaches aim to enhance immunogenic responses and offer hope for better outcomes in this challenging malignancy.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"149 ","pages":"Article 107653"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143007867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-term follow-up of zimberelimab in relapsed or refractory classic Hodgkin lymphoma: Insights from the phase Ⅱ YH-S001-04 clinical trial","authors":"Suisui Kan ,&nbsp;Hai Bai ,&nbsp;Hui Liu ,&nbsp;Jie Cui ,&nbsp;Xiaoyan Ke ,&nbsp;Huilai Zhang ,&nbsp;Lihong Liu ,&nbsp;Dongmei Yan ,&nbsp;Yongsheng Jiang ,&nbsp;Aimin Zang ,&nbsp;Junyuan Qi ,&nbsp;Li Wang ,&nbsp;Zhuogang Liu ,&nbsp;Bing Xu ,&nbsp;Ying Zhang ,&nbsp;Zhihui Zhang ,&nbsp;Xielan Zhao ,&nbsp;Chunhong Hu ,&nbsp;Shenmiao Yang ,&nbsp;Hui Zhou ,&nbsp;Mingzhi Zhang","doi":"10.1016/j.leukres.2024.107633","DOIUrl":"10.1016/j.leukres.2024.107633","url":null,"abstract":"<div><h3>Background</h3><div>Treating relapsed or refractory classical Hodgkin lymphoma (R/R cHL) remains challenging. This report extends the three-year follow-up period for the phase Ⅱ YH-S001–04 trial, expanding upon the initial 15.8-month analysis.</div></div><div><h3>Methods</h3><div>Zimberelimab 240 mg was administered every two weeks for two years or until disease progression or death. The endpoint was the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety.</div></div><div><h3>Results</h3><div>The median follow-up was 38.0 months (3.5–42.8 months). The ORR was 91.6 % (95 % CI, 83.8–95.9). Median PFS was 23.6 months, with a longer PFS in responders (28.5 months) compared to non-responders (9.2 months) (<em>P</em>=0.0098). Complete responders had longer mPFS than partial responders (Not reached vs. 28.5 months, <em>P</em>=0.3469). Relapsed patients had improved mPFS compared to refractory cHL (23.6 vs. 10.6 months, <em>P</em>=0.0061). Patients with ＜3 lines of therapy showed longer mPFS compared to ≥3 lines (not reached vs. 23.6 months, <em>P</em>=0.0095). The 3-year OS rate was 94.0 % (95 % CI, 85.9–97.4). No serious adverse events with incidence &gt;5 %.</div></div><div><h3>Conclusions</h3><div>With encouraging data on both PFS and OS, zimberelimab demonstrates ongoing efficacy and safety in treating R/R cHL, supporting zimberelimab as an effective treatment alternative for R/R cHL (NCT03655483).</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"149 ","pages":"Article 107633"},"PeriodicalIF":2.1,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971414","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":"Trends of changes in human T-cell leukemia virus type 1 epidemiology in Japan and globally","authors":"Noriaki Yoshida ,&nbsp;Ayumi Hida ,&nbsp;Ritsu Sakata","doi":"10.1016/j.leukres.2025.107654","DOIUrl":"10.1016/j.leukres.2025.107654","url":null,"abstract":"<div><div>Human T-cell leukemia virus type 1 (HTLV-1) has been identified as a cause of adult T-cell leukemia-lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Despite several HTLV-1 endemic areas being identified, comprehensive investigations have yet to be conducted in all the regions of the world. This review aims to summarize the current reports on HTLV-1. As vertical transmission is known to be a risk factor for ATL development, prevention strategies have been initiated in Japan, and these efforts may be related to the decrease in the estimated number of HTLV-1 carriers in Japan. In numerous HTLV-1 endemic regions, the prevalence of HTLV-1 increases with age, which may be attributed to horizontal infection. However, the incidence of HTLV-1 infection appears to be high among adolescents and young adults in Japan, especially in non-endemic areas. The clinical significance of HTLV-1 infections, other than ATL and HAM/TSP, has recently been documented. Consequently, it is imperative to develop treatment strategies for HTLV-1 infections, including measures to prevent horizontal infections.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"150 ","pages":"Article 107654"},"PeriodicalIF":2.1,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143154627","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":"Optimal therapeutic strategies in relapsed/refractory AML with prior exposure to venetoclax-based therapy","authors":"Sawyer Bawek,&nbsp;Matthew Burwinkel,&nbsp;Prutha Patel,&nbsp;Katy Wang,&nbsp;Kristopher Attwood,&nbsp;Tara Cronin,&nbsp;Melissa Fos,&nbsp;Steven Green,&nbsp;Pamela J. Sung,&nbsp;James E. Thompson,&nbsp;Elizabeth A. Griffiths,&nbsp;Eunice S. Wang,&nbsp;Amanda C. Przespolewski","doi":"10.1016/j.leukres.2025.107643","DOIUrl":"10.1016/j.leukres.2025.107643","url":null,"abstract":"","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"150 ","pages":"Article 107643"},"PeriodicalIF":2.1,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143378234","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":"Blood cancer therapy with synthetic receptors and CRISPR technology","authors":"Haiying Zhang ,&nbsp;Mingxin Zhong ,&nbsp;Jingdong Zhang ,&nbsp;Changkun Chen","doi":"10.1016/j.leukres.2025.107646","DOIUrl":"10.1016/j.leukres.2025.107646","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR)-T and -NK cells showed great success in treating hematological malignancies, including leukemia, lymphoma, and myeloma. CRISPR technology and other synthetic receptors (GPCR and synNotch) have helped to address some of the limitations and challenges associated with CAR-based therapies. Herein, this review aims to discuss how CAR can be integrated with other synthetic receptors and various CRISPR/Cas tools for blood cancer therapy. CAR-expressing cells equipped with other synthetic receptors can conditionally execute tumoricidal functions, prevent tumor escape from immune surveillance, and minimize non-tumor off-target toxicity. We also discussed how various CRISPR-Cas tools can be harnessed to enhance CAR cells functionality and persistence. The advances, pitfalls, and future perspectives for these synthetic receptors and CRISPR technology in blood cancer therapy are comprehensively discussed.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"150 ","pages":"Article 107646"},"PeriodicalIF":2.1,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143229974","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":"The increase in the expression of circRNAs may contributes to a poor prognosis in acute myeloid leukemia: A systematic review and meta-analysis","authors":"Meng Li ,&nbsp;Shiming Zhang ,&nbsp;Junfan Wei ,&nbsp;Mengfei Liu ,&nbsp;Bohao Zhang ,&nbsp;Shen Li ,&nbsp;Yue Xiao ,&nbsp;Yuandong Yu ,&nbsp;Ruipeng Song","doi":"10.1016/j.leukres.2024.107639","DOIUrl":"10.1016/j.leukres.2024.107639","url":null,"abstract":"<div><h3>Objective</h3><div>The primary methods for defining the prognostic risk of AML patients are cytogenetic and molecular analysis at the time of diagnosis. However, the prognosis of intermediate-risk patients is still not well assessed for biomarkers. The main objective of this meta-analysis is to evaluate the relationship between circRNAs and AML prognosis, to provide a theoretical basis for finding effective prognostic indicators in intermediate-risk patients, and to provide an important scientific basis for the development or revision of WHO practice guidelines and ELN risk classification, and to highlight the importance of continuing to focus on and evaluate the prognostic impact of circRNAs on AML in future studies.</div></div><div><h3>Methods</h3><div>We performed a comprehensive literature search across PubMed, the Cochrane Library, and Web of Science databases for studies published up to September 15, 2024. Articles were selected based on inclusion criteria. The Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of studies. The outcome measure of overall survival (OS) was used, and hazard ratios (HR) and 95 % confidence intervals (CI) were pooled to estimate the relationship between circRNA expression and prognosis in AML using STATA 17.0 software.</div></div><div><h3>Results</h3><div>A total of 13 studies involving 1401 AML patients were included. The studies showed a significantly increased hazard ratio (HR) of upregulated CircRNA expression for OS (HR=1.87, 95 % CI=1.51–2.32, <em>P</em> &lt; 0.001). The results of subgroups analysis showed a significant increase in the hazard ratio (HR) for upregulation of CircRNA expression in EFS and circ_0012152（HR= 1.66, 95 % CI= 1.19–2.32, <em>P</em> &lt; 0.005 and HR= 2.26,95 % CI= 1.27–4.00, <em>P</em> &lt; 0.005), respectively. No significant heterogeneity or publication bias was detected.</div></div><div><h3>Conclusion</h3><div>Upregulated circRNA expression is significantly associated with poor prognosis in AML patients and may serve as a prognostic marker for AML.</div></div>","PeriodicalId":18051,"journal":{"name":"Leukemia research","volume":"148 ","pages":"Article 107639"},"PeriodicalIF":2.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872281","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}