Aim of this study is to investigate the outcome of NGS MRD based risk stratified treatment for standard risk acute lymphoblastic leukemia in children and adolescents.

开始日期2024-03-05

申办/合作机构

Samsung Medical Center

NCT05681260

/ Recruiting临床3期IIT

A Randomized Trial Using a Modified COG ABFM Regimen Backbone to Investigate Capizzi Escalating Methotrexate Versus High Dose Methotrexate in Children with Newly Diagnosed T-cell Lymphoblastic Lymphoma (T-LBL)

T-cell lymphoblastic lymphoma (T-LBL) is the second most common subtype of non-Hodgkin lymphoma (NHL) in children and adolescents. With current treatment, event-free survival (EFS) rates vary between 75%
85%. Two different MTX intensification strategies are used commonly: HD-MTX with leucovorin rescue, and Capizzi-style MTX without leucovorin rescue plus PEG-ASP (C-MTX). Although superior outcome of patients with T-ALL receiving C-MTX compared with HD-MTX on the AALL0434 trial, the 2 approaches had not been compared directly in patients with T-LBL. There remains controversy on PET/CT interpretation in children with NHL. Large prospective studies in pediatric patients with T-LBL regarding PET/CT value for this is scarce. Around 1% pediatric patients with T-LBL will not achieve remission at the end of Induction (induction failure). The optimal treatment for this small subgroup is largely unclear. The BFM HR Blocks usually are applied to these patients even though the efficacy is unknown. Novel targeted therapies are needed for use. Dasatinib is identified as a targeted therapy for T-cell ALL in preclinical drug screening.

开始日期2023-02-06

申办/合作机构

上海交通大学医学院附属上海儿童医学中心

[+14]

NCT04440267

/ Not yet recruiting临床2期IIT

A Prospective, Single Arm, Open Label, Clinical Trial to Evaluate the Efficacy of Acute Lymphoblastic Leukemia-Based Therapy in Treating Patients With Acute Leukemia of Ambiguous Lineage

In this prospective, single arm, open label, clinical trial, a total of 50 acute leukemia of ambiguous lineage patients will be enrolled. Patients will receive acute lymphoblastic leukemia (ALL) -based chemotherapy and are permitted to receive allogeneic hematopoietic stem cell transplantation (HSCT) after CR . Otherwise, they will finish the consolidation chemotherapy. Patients with t(9;22) will receive chemotherapy combined with tyrosine kinase inhibitors. The purpose of current study is to evaluate the clinical efficacy of ALL-based chemotherapy，effect of genetic abnormality and minimal residual disease (MRD) on prognosis in patients with acute leukemia of ambiguous lineage.

开始日期2020-06-20

申办/合作机构-

100 项与 L-门冬酰胺酶相关的临床结果

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100 项与 L-门冬酰胺酶相关的转化医学

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100 项与 L-门冬酰胺酶相关的专利（医药）

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项与 L-门冬酰胺酶相关的文献（医药）

2025-08-01·Current Drug Safety

Posterior Reversible Encephalopathy Syndrome Associated with L-Asparaginase Treatment in Children: Literature Review and Six Case Reports

Article

作者: Perez, Maria MargaritaTosta ; Belen, Lisandra Herrera ; Pessoa, Adalberto ; Avendano, Jorge Farias

:L-asparaginase (L-ASNase) is an enzyme that shows targeted activity against Acute Lymphoblastic Leukemia (ALL) and similar lymphoid neoplasms by facilitating the breakdown of asparagine into L-aspartic acid, thereby reducing L-asparagine levels in leukemic cells. However, its therapeutic potential is hindered by its associated toxicity, leading to complications, such as thrombosis, hemorrhage, thrombocytopenia, fibrinolysis, hypersensitivity reactions, and the development of Posterior Reversible Encephalopathy Syndrome (PRES). This review compiles documented cases of PRES linked to treating B and T cell acute lymphoblastic leukaemia in children using L-ASNase. Although this pathology is rare, understanding its management is crucial within ASNase-based chemotherapy protocols. As PRES lacks a specific treatment, focusing on symptomatic management becomes pivotal. Therefore, comprehending the underlying causes during L-ASNase treatment for acute lymphoblastic leukemia is essential. Understanding the etiology and clinical symptoms of this illness is critical for early diagnosis and treatment.:The cases of PRES described in this review include instances in which this syndrome has appeared after the administration of L-ASNase in children. In some cases, PRES developed during induction therapy, while in others, it occurred during the reinduction phase. These cases resolved days after discontinuation of L-ASNase. The findings suggest a close relationship between drug administration and the appearance of brain lesions, as evidenced by the disappearance or decrease of these lesions when the drug was eliminated from the bloodstream.

2025-06-01·Pediatric Blood & Cancer

Amino Acid Stress Response Genes Contribute to a 25‐Fold Increased Risk of L‐Asparaginase–Induced Hypersensitivity

Article

作者: Scott, Erika N. ; Chang, Wan‐Chun ; Trueman, Jessica N. ; Anderson, Spencer J. ; Córdova‐Delgado, Miguel ; Raack, Edward J. ; Carleton, Bruce C. ; Rassekh, S. Rod. ; Loucks, Catrina M. ; Ross, Colin J. D.

ABSTRACTBackgroundL‐asparaginase is essential in treating pediatric acute lymphoblastic leukemia (ALL) but is limited by hypersensitivity reactions in up to 70% of patients, leading to severe, dose‐limiting complications and compromised event‐free survival.ProcedureThis study conducted a genome‐wide association study (GWAS) in a discovery cohort of 221 pediatric cancer patients who experienced l‐asparaginase–induced hypersensitivity reactions (≥CTCAE grade 2) and 705 controls without hypersensitivity despite equivalent exposure. Results were replicated in an independent cohort of 41 cases and 139 controls.ResultsSignificant associations were identified between hypersensitivity and four genes crucial for amino acid stress response: CYP1B1 (rs59569490; odds ratio [OR] = 8.5; 95% confidence interval [CI], 3.9–18.5; p = 1.5 × 10−10), SEC16B (rs115461320; OR = 4.2; 95% CI, 2.5–7.9; p = 1.2 × 10−6), OPLAH (rs11993268; OR = 4.8; 95% CI, 2.4–9.9; p = 2.0 × 10−6), and SORCS2 (rs11940340; OR = 6.7; 95% CI, 2.8–15.7; p = 5.7 × 10−7). Variants in SEC16B, OPLAH, and SORCS2 remained significant in the analysis of the replication cohort (p < 0.05). Patients who carried risk alleles in two or more of these genes experienced an 86.4% increased incidence of hypersensitivity reactions in the discovery cohort (OR = 25.2; 95% CI, 7.4–86.2; p = 1.0 × 10−10), which was replicated in the independent cohort with a 100% incidence in carriers (p = 0.04).ConclusionsThe cumulative incidence of these large effect variants highlights their significance for the identification of patients at high risk of l‐asparaginase–induced hypersensitivity. Successfully identifying patients at increased risk of hypersensitivity reactions can inform personalized treatment strategies and limit these harmful dose‐limiting reactions in pediatric ALL.

2025-06-01·Biochimie

Cloning, Expression, Characterization and in silico studies of l-asparaginase from Vibrio sp. (GBPx3)

Article

作者: Eslami, Solat ; Mahboudi, Hossein ; Asad, Sedigheh ; Natanzi, Sareh Sadat Mousavi

l-asparaginase is a critical therapeutic enzyme for treating acute lymphoblastic leukemia (ALL), a common childhood malignancy. In this study, the l-asparaginase coding sequence from halophilic Vibrio sp. (GBPx3) was cloned, expressed in Escherichia coli, and characterized. The enzyme exhibited a molecular weight of 39.2 kDa and demonstrated a K_m of 4.517 mM, k_cat of 2.88 1/s, and V_max of 0.1055 μmol/min, reflecting high specificity for l-asparagine and minimal activity (0.4 %) toward l-glutamine. Optimal activity was observed at physiological conditions (37 °C, pH 7.5 and 125-150 mM NaCl), consistent with human serum osmolality. The half-life of the enzyme was 2.64 h in human serum at 37 °C that is longer than the half-life reported for E. colil-asparaginase. Additionally, the enzyme had no toxic impact on human umbilical vein endothelial cells (HUVEC) and human erythrocytes. The recombinant l-asparaginase was predicted to be 29.3 % helix, 35.6 % turns, and 35.1 % random by circular dichroism spectroscopy. AlphaFold predicted a 3D structure with promising validation scores. The molecular docking study showed that Thr14, Ser60, Thr91, and Asp92 are putative active site residues, with a negative binding energy of -4.5 kJ/mol for the substrate-enzyme interaction. The enzyme's low immunogenicity, high serum stability, and reduced glutaminase activity highlight its potential as a safer therapeutic alternative. Future experiments and protein engineering studies are needed to explore enzyme's in vivo efficacy and improve its clinical effectiveness.

项与 L-门冬酰胺酶相关的新闻（医药）

2024-12-10

·PRNewswire

Antengene Presents Results from Two Late-Stage Clinical Studies of Selinexor at ASH 2024

SHANGHAI and HONG KONG, Dec. 9, 2024 /PRNewswire/ -- Antengene Corporation Limited ( "Antengene", SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class medicines for hematologic malignancies and solid tumors, today announced that it presented the latest data from two clinical studies of selinexor in two posters at the 2024 American Society of Hematology Annual Meeting (ASH 2024). Details on the Posters: Title: Weekly Selinexor, Bortizomib and Dexamethasone (SVd) Versus Twice Weekly Bortizomib and Dexamethasone (Vd) in Chinese Patients with Relapsed and Refractory Multiple Myeloma (RRMM): Primary Analysis of Phase III Bench Study Publication Number: 4748 Session: 654. Multiple Myeloma: Pharmacologic Therapies: Poster III Date: Monday, December 9, 2024 Time: 6:00 PM - 8:00 PM (Pacific time) 10:00 AM - 12:00 PM, December 10, 2024 (Beijing time) The BENCH study is a Phase III randomized, open-label, multicenter clinical trial, aiming to evaluate the efficacy and safety of selinexor, bortezomib and dexamethasone (SVd) regimen against bortezomib and dexamethasone (Vd) regimen in Chinese adult patients with R/R MM who have received one to three prior lines of therapy. At present, a New Drug Application (NDA) based this study has already been submitted to and accepted by China's National Medical Products Administration (NMPA). As of May 9, 2024, a total of 154 Chinese R/R MM patients were randomized to SVd group (n=101) or Vd group (n=53) and 152 patients received at least one dose of study drug (safety population). Efficacy results showed that the median progression-free survival (mPFS) was 8.1 months with SVd group and 6.3 months with Vd group. The overall response rate (ORR) was higher in SVd group than in Vd group. SVd group had a significantly higher proportion of patients with a very good partial response (VGPR) or better responses. The median time to response and the median duration of response were 0.8 vs 1.4 months and 9.7 vs 7.2 months (SVd vs Vd), respectively. During the study, some subjects experienced treatment emergent adverse events (TEAEs). The most frequent Grade 3-4 adverse events (AEs) for SVd and Vd (≥10%) included thrombocytopenia, lymphocytopenia, and anemia. The incidence of Grade≥2 peripheral neuropathy (PN) was significantly lower in SVd than in Vd group. The BENCH study has met its primary and key secondary endpoints, with results consistent with the BOSTON study. These results showed that the SVd regimen decreased the risk of progression and obtained much more profound responses compared to standard Vd regimen in Chinese patients with R/R MM. The incidence of Grade ≥2 PN were significantly reduced. Title: Selinexor Combined with Tislelizumab in Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma (R/R ENKTL): Preliminary Results of Arm C, from a Multicenter, Single-Arm, Phase I/II Study, Touch Publication Number: 4448 Session: 625. T Cell, NK Cell, or NK/T Cell Lymphomas: Clinical and Epidemiological: Poster III Date: Monday, December 9, 2024 Time: 6:00 PM - 8:00 PM (Pacific time) 10:00 AM - 12:00 PM, December 10, 2024 (Beijing time) The Phase I/II TOUCH study is investigating selinexor combined with different drugs in R/R ENKTL. Arm C of the study aims to evaluate the safety, tolerability and preliminary efficacy of selinexor in combination with anti-PD-1 antibody tislelizumab. As of 18 May 2024, 17 R/R ENKTL patients were enrolled in Arm C [Sel 40mg (n=3); Sel 60mg (n=14)]. Sixteen patients previously exposed to both L-asparaginase (L-Asp) and checkpoint inhibitors (CPIs) including 8 patients who had received prior Tislelizumab (Tis); eleven (64.7%) patients were refractory to their last-line therapy. Efficacy results showed that, of 16 CPIs exposed patients (one patient was efficacy non-evaluable), the ORR was 75% (12/16), including 7 CRs and 5 PRs; and the median PFS was 6.7 months (95% CI 1.5, NE). During the study, all patients experienced TEAEs. The most common TEAEs included anemia, neutropenia, asthenia, decreased appetite, weight loss, and thrombocytopenia. Ten patients (58.8%) experienced Grade≥3 TEAEs. Treatment emergent serious adverse events (TESAEs) occurred in 4 patients (23.5%), of which two were considered treatment related. No patient discontinued due to TEAEs. Most of toxicities were manageable by dose modification and supportive care. In the study, the chemo-free regimen, Sel plus Tis, showed a favorable response rate and manageable safety profile in R/R ENKTL. This approach may probably reverse drug resistance in ENKTL that has progressed after prior CPI treatment. About Antengene Antengene Corporation Limited ( "Antengene", SEHK: 6996.HK) is a leading commercial-stage R&D-driven global biopharmaceutical company focused on the discovery, development, manufacturing and commercialization of innovative first-in-class/best-in-class therapeutics for the treatment of hematologic malignancies and solid tumors, in realizing its vision of "Treating Patients Beyond Borders". Since 2017, Antengene has built a pipeline of 9 oncology assets at various stages going from clinical to commercial, including 6 with global rights, and 3 with rights for the APAC region. To date, Antengene has obtained 31 investigational new drug (IND) approvals in the U.S. and Asia, and submitted 10 new drug applications (NDAs) in multiple Asia Pacific markets, with the NDA for XPOVIO® (selinexor) already approved in Mainland of China, Taiwan China, Hong Kong China, Macau China, South Korea, Singapore, Malaysia, Thailand and Australia. Forward-looking statements The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, we undertake no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development. For a further discussion of these and other factors that could cause future results to differ materially from any forward-looking statement, please see the other risks and uncertainties described in the Company's Annual Report for the year ended December 31, 2023, and the documents subsequently submitted to the Hong Kong Stock Exchange. For more information, please contact: Investor Contacts: Donald Lung E-mail: [email protected] Mobile: +86 18420672158 PR Contacts: Peter Qian E-mail: [email protected] Mobile: +86 13062747000 SOURCE Antengene Corporation Limited WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床结果临床3期申请上市上市批准ASH会议

2024-12-06

·学术经纬

Cancer Discovery｜儿童急性T淋巴细胞白血病的临床特征与高危突变

撰文 | 尹彤责编 | 周叶斌急性T淋巴细胞白血病（T-ALL）是儿童最常见的血液系统肿瘤之一。其中γδ T-ALL是一个较少研究的亚型，其肿瘤细胞表面表达由γ链和δ链组成的T细胞受体（TCR），约占全部T-ALL病例的10%。既往研究提示，该亚型可能面临更差的治疗效果和更高的复发风险。由于缺乏大规模针对γδ T-ALL的研究，其临床特征和发病机制仍不清楚。虽然近年来通过基因组学研究取得了一些进展，但这些研究纳入的γδ T-ALL病例较少，且缺乏对非编码区等基因组特征的分析，因此亟需进行更全面、深入的研究。近日，以圣裘德儿童研究医院 Charles G. Mullighan 和 Hiroto Inaba 团队牵头的多国联合团队在 Cancer Discovery 发表了题为 Biologic and Clinical Analysis of Childhood Gamma Delta T-ALL Identifies LMO2/STAG2 Rearrangements as Extremely High Risk 的文章。该研究基于200例γδ T-ALL的临床和基因组数据，揭示了发病年龄<3岁、诱导治疗后MRD≥1%和STAG2/LMO2突变是儿童γδ T-ALL的高危因素，进而筛选了针对此类患者有效的治疗策略。本研究纳入了由13项临床研究组成的多国合作组的200例25岁以下的γδ T-ALL患者，以及1,067例根据治疗方案匹配的非γδ T-ALL对照病例。研究发现，γδ T-ALL患者总体上表现出较差的预后，诊断年龄更小，且治疗后的应答更差，表现为在诱导治疗和巩固治疗后都有更高的微小残留病变（measurable residual disease，MRD）水平，需要进行造血干细胞移植的比例更高，且原发病或治疗副作用造成的死亡率更高。诊断年龄小于3岁的γδ T-ALL患者，其5年无事件生存率（event-free survival，EFS）仅为33%，总生存率（overall survival，OS）仅为49%，显著低于诊断年龄≥3岁的γδ T-ALL患者或非γδ T-ALL患者。此外，诱导治疗结束时（end of induction，EOI），MRD≥1%的患者在所有年龄段的生存率均显著低于MRD<1%的患者。这些数据表明诊断年龄 <3岁和 EOI 时 MRD≥1% 是提示 γδ T-ALL 患儿不良预后的高危因素，因此这些高风险患者可能需要优化的治疗方案。此外，研究发现，γδ T-ALL患者的复发主要局限于骨髓（骨髓复发率高达91.3%），而非γδ T-ALL患者中枢神经系统复发更常见。研究设计和患者临床结局：（A）研究方案，（B）γδ T-ALL患者与非γδ T-ALL患者的生存率对比，（C/D）γδ T-ALL患者中诊断年龄和EOI时MRD水平对生存率的影响结合全基因组测序（whole genome sequencing，WGS）、RNA测序和HiChIP等技术，研究者对γδ T-ALL患者的基因变异进行了分型，并解析了突变导致的疾病机制。γδ T-ALL患者与非γδ T-ALL患者相比具有独特的基因型分布。STAG2/LMO2双突变是γδ T-ALL患者特征性变异之一，所有纳入研究的该亚型γδ T-ALL患儿的诊断年龄都小于3岁，且与其他类型患者相比生存期显著较短。进一步研究表明STAG2/LMO2双突变患者中最常见的变异类型是LMO2::STAG2重排，导致STAG2失活和LMO2过度激活。STAG2是黏着复合物（cohesin complex）的重要组分，参与染色质空间折叠以形成拓扑相关结构域（topologically associating domain，TAD），进而通过增强子-启动子相互作用调控基因正常表达。通过构建STAG2缺失和过表达的细胞模型，并进行RNA-seq和H3K27ac ChIP-seq分析，研究者证明了STAG2失活将导致TAD结构异常，严重破坏T细胞分化相关基因表达，导致白血病的发生。此外，研究还发现了其他γδ T-ALL特异性基因分型，如LMO2-γδ样、超二倍体T-ALL伴重现性染色体增加、TLX3重排和PICALM::MLLT10融合等，这些亚型γδ T-ALL患者具有各自不同的临床特征。 γδ T-ALL基因分型和临床特征：（A）参考所有T-ALL基因组数据对γδ T-ALL进行基因分型，（B）不同基因型在γδ T-ALL与非γδ T-ALL患者中的分布，（D）γδ T-ALL患者不同基因型与诊断年龄的关系，（E）不同基因型γδ T-ALL患者的生存曲线最后，研究者通过高通量药物筛选探索了潜在的治疗策略。PARP抑制剂talazoparib和组蛋白去乙酰化酶抑制剂vorinostat是对STAG2/LMO2 γδT-ALL细胞具有显著杀伤作用的药物，其中PARP抑制剂靶向STAG2失活造成的DNA复制缺陷，使双链DNA断裂积累并诱导细胞死亡。在患者来源的异种移植模型（PDX）中，talazoparib 和 vorinostat 都可以有效地抵抗肿瘤生长。其他有效的药物包括nelarabine和L-门冬酰胺酶等，这些药物都已经被用于T-ALL或其他肿瘤的临床研究或治疗。此发现为高风险的γδ T-ALL患儿提供了一种潜在的精准治疗策略。针对talazoparib（Tal）和vorinostat（Vor）的临床前试验表明两种药物均能够显著抑制PDX肿瘤细胞的生长总之，本研究首次全面探讨了儿童γδ T-ALL的临床特征和基因分型，并揭示了高危突变的致病机制及潜在的治疗策略。研究明确了诊断年龄和MRD水平对患者预后的关键作用，并揭示了高危患儿STAG2失活对染色质结构和基因表达具有深远影响。更重要的是，本研究提出了 PARP 抑制剂等可做为靶向 STAG2/LMO2 亚型的潜在治疗策略，这些成果加深了对儿童γδ T-ALL的认识，也为未来γδ T-ALL患儿的风险分层和个体化治疗开发提供了重要参考。撰文责编制作排版 | Sheila 校对 | uu 延伸阅读儿童T细胞急性淋巴细胞白血病的多组学分析竺晓凡/张英驰团队揭示儿童T-ALL癌细胞克隆演化模式及耐药新机制 *本文由深圳市拾玉儿童公益基金会“儿童肿瘤前沿”团队编译或约稿，文中图表均源引自文献原文。本文著作权归文章作者所有，欢迎个人转发分享，未经允许禁止转载，作者拥有所有法定权利，违者必究。如需转载，请留言或联系shiyu@curekids.cn。本文旨在分享儿童肿瘤科研前沿成果，不是治疗方案推荐。如需获得疾病治疗方案指导，请前往正规医院就诊。 ▼滑动查看更多▼ 原文摘要（Abstract） Acute lymphoblastic leukemia expressing the gamma delta T-cell receptor (γδ T-ALL) is a poorly understood disease. We studied 200 children with γδ T-ALL from 13 clinical study groups to understand the clinical and genetic features of this disease. We found age and genetic drivers were significantly associated with outcome. γδ T-ALL diagnosed in children under 3 years of age was extremely high-risk and enriched for genetic alterations that result in both LMO2 activation and STAG2 inactivation. Mechanistically, using patient samples and isogenic cell lines, we show that inactivation of STAG2 profoundly perturbs chromatin organization by altering enhancer-promoter looping, resulting in deregulation of gene expression associated with T-cell differentiation. High-throughput drug screening identified a vulnerability in DNA repair pathways arising from STAG2 inactivation, which can be targeted by poly(ADP-ribose) polymerase inhibition. These data provide a diagnostic framework for classification and risk stratification of pediatric γδ T-ALL. Significance: Patients with acute lymphoblastic leukemia expressing the gamma delta T-cell receptor under 3 years old or measurable residual disease ≥1% at end of induction showed dismal outcomes and should be classified as having high-risk disease. The STAG2/LMO2 subtype was enriched in this very young age group. STAG2 inactivation may perturb chromatin conformation and cell differentiation and confer vulnerability to poly(ADP-ribose) polymerase inhibition. DOI: 10.1158/2159-8290.CD-23-1452 👇点击此处，直达原文

细胞疗法临床结果免疫疗法临床研究信使RNA

2024-01-09

·Science Daily

The hidden identity of leukemia

Researchers used various sequencing technologies to explore the molecular characteristics of myeloid/natural killer cell precursor acute leukemia (MNKPL). They observed activation of the NOTCH1 and RUNX3 genes, with lower expression of the BCL11B gene. MNKPL cells were also highly sensitive to a drug called L-asparaginase. Collectively, these qualities make MNKPL distinct from other leukemia types. These insights will assist with more accurate clinical diagnoses and therapeutic development for MNKPL. Leukemia is a common term used to refer to a form of blood cancer. However, there are different types of leukemia depending on the cell type involved. One unique form is myeloid/natural killer (NK) cell precursor acute leukemia (MNKPL). Because of its rarity, there is no consensus on the specific characteristics needed to clinically identify this disease. In a recent article published in Science Advances, a team led by researchers at Tokyo Medical and Dental University (TMDU) used various approaches to better assess the molecular pro drug sensitivity characteristics of MNKPL. MNKPL was only first proposed as a leukemia subtype in 1997. Extramedullary involvement is one of the hallmarks of MNKPL. It is prevalent in East Asian countries. Although the immunological phenotype of MNKPL was explored previously, a full genetic characterization of this cancer type had not been performed. These details would help support more accurate diagnoses for patients, which would lead to more appropriate therapeutic decisions. Therefore, the TMDU group aimed to investigate MNKPL on a single-cell level. "A single-cell exploration of MNKPL would not only help us better understand its clinical and genomic features, but also clarify the specific cellular origin of this disease," says Dr. Akira Nishimura, lead author of the study. The team first used what is known as a multiomics approach to investigate MNKPL patient samples. They used various sequencing technologies to determine if there were any relevant mutations in specific genes, look for expression differences in certain signaling pathways at the RNA level, and examine any unique DNA methylation patterns. "Our results demonstrate that MNKPL has molecular qualities that are distinct from other similar cancers, such as acute myeloid leukemia, T-cell acute lymphoblastic leukemia, and mixed-phenotype acute leukemia," explains Dr. Masatoshi Takagi, senior author. "Specific hallmarks of MNKPL include activation of the NOTCH1 and RUNX3, as well as lower expression of the BCL11B." Further work at the single-cell level in MNKPL cells showed that NK cells and myeloid cells come from a common progenitor cell type. The researchers also conducted in vitro drug sensitivity assays where they measured MNKPL cell responses to 79 individual anti-cancer drugs. "We observed that MNKPL cells were highly sensitive to a drug called L-asparaginase, which has already shown clinical effectiveness for this disease," says Dr. Nishimura. "Mechanistically, we found that this was from low expression of asparagine synthetase, a quality that was distinct from other similar types of leukemia." Overall, the robust and comprehensive analysis performed in this study provides crucial molecular details for characterizing MNKPL. This work will undoubtedly help clinicians more effectively diagnose MNKPL and choice of therapeutic option. Additionally, this work provides data that will assist with novel therapeutic target identification and drug development in this leukemia.

细胞疗法

100 项与 L-门冬酰胺酶相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	L01XX02	DB00023

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
急性和慢性白血病	韩国	Kyowa Kirin Korea Co., Ltd.	1993-03-19
急性淋巴细胞白血病	日本	Kyowa Kirin Co., Ltd.	1971-06-25
淋巴瘤	日本	Kyowa Kirin Co., Ltd.	1971-06-25

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


EHA2021	N/A	急性淋巴细胞白血病	316	L-asparaginase	(窪衊壓鏇顧憲壓鹹餘齋) = 製鏇鬱蓋觸衊艱繭壓衊願範餘積製壓襯顧廠淵 (廠夢繭艱糧製築齋鑰顧 ) 更多	-	2021-06-09
ISTH2020	N/A	急性淋巴细胞白血病	-	L-Asparaginase	願鹹繭醖積鏇齋觸願範(網顧鏇築糧衊築齋鬱壓) = 蓋醖夢獵築觸願窪襯夢範顧願艱鏇衊構願餘積 (鹹糧廠壓鹹齋齋蓋簾獵 ) 更多	-	2020-07-12
Peking University Cancer Hospital (ICML2017)	N/A	结外NK-T细胞淋巴瘤一线	196	L-asparaginase (CHOP-like)	鏇積積構觸簾齋顧膚繭(獵簾遞窪觸築艱構鬱齋) = 鹹淵顧廠繭壓窪選鑰淵淵願製遞壓願遞憲獵網 (壓選鏇簾製遞繭網簾夢 ) 更多	积极	2017-06-07
Peking University Cancer Hospital (ICML2017)	N/A	结外NK-T细胞淋巴瘤一线	196	L-asparaginase (CHOP-L)	鏇積積構觸簾齋顧膚繭(獵簾遞窪觸築艱構鬱齋) = 簾鬱繭淵齋壓膚鹹醖鹹淵願製遞壓願遞憲獵網 (壓選鏇簾製遞繭網簾夢 ) 更多	积极	2017-06-07
ICML2015	临床1/2期	难治性弥漫性大 B 细胞淋巴瘤 MYC-rearranged \| ki67	9	l-asparaginase	衊廠夢製鏇窪願壓簾糧(鹽繭蓋壓夢顧網鹹網膚) = Grade 3 hepatic toxicity occurred in one patient during the first cycle 淵餘醖繭餘選選窪壓窪 (窪憲製蓋繭願膚齋選壓 ) 更多	积极	2015-06-09
AACR2010	N/A	肥胖一线	7	L-asparaginase (Lean subjects)	遞憲襯構艱壓窪鹽壓繭(襯繭願選鹹蓋觸選壓壓) = 觸製繭鹹鏇顧積鏇鏇願網製簾獵鏇顧壓艱製選 (獵獵餘襯簾積襯窪窪簾 ) 更多	-	2010-04-15
AACR2010	N/A	肥胖一线	7	L-asparaginase (Obese subjects)	遞憲襯構艱壓窪鹽壓繭(襯繭願選鹹蓋觸選壓壓) = 鏇襯糧衊廠觸鹹膚築齋網製簾獵鏇顧壓艱製選 (獵獵餘襯簾積襯窪窪簾 ) 更多	-	2010-04-15