{"title":"超越 B 细胞急性淋巴细胞白血病的基因亚型:基于路径的精准肿瘤学患者分层。","authors":"Ozlem Ulucan","doi":"10.1089/omi.2024.0145","DOIUrl":null,"url":null,"abstract":"<p><p>Precision oncology promises individually tailored drugs and clinical care for patients with cancer: That is, \"the right drug, for the right patient, at the right dose, and at the right time.\" Although stratification of the risk for treatment resistance and toxicity is key to precision oncology, there are multiple ways in which such stratification can be achieved, for example, genetic, functional pathway based, among others. Moving toward precision oncology is sorely needed in the case of acute lymphoblastic leukemia (ALL) wherein adult patients display survival rates ranging from 30% to 70%. The present study reports on the pathway activity signature of adult B-ALL, with an eye to precision oncology. Transcriptome profiles from three different expression datasets, comprising 346 patients who were adolescents or adults with B-ALL, were harnessed to determine the activity of signaling pathways commonly disrupted in B-ALL. Pathway activity analyses revealed that Ph-like ALL closely resembles Ph-positive ALL. Although this was the case at the average pathway activity level, the pathway activity patterns in B-ALL differ from genetic subtypes. Importantly, clustering analysis revealed that five distinct clusters exist in B-ALL patients based on pathway activity, with each cluster displaying a unique pattern of pathway activation. Identifying pathway-based subtypes thus appears to be crucial, considering the inherent heterogeneity among patients with the same genetic subtype. In conclusion, a pathway-based stratification of the B-ALL could potentially allow for simultaneously targeting highly active pathways within each ALL subtype, and thus might open up new avenues of innovation for personalized/precision medicine in this cancer that continues to have poor prognosis in adult patients compared with the children.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":null,"pages":null},"PeriodicalIF":4.6000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Expanding Beyond Genetic Subtypes in B-Cell Acute Lymphoblastic Leukemia: A Pathway-Based Stratification of Patients for Precision Oncology.\",\"authors\":\"Ozlem Ulucan\",\"doi\":\"10.1089/omi.2024.0145\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Precision oncology promises individually tailored drugs and clinical care for patients with cancer: That is, \\\"the right drug, for the right patient, at the right dose, and at the right time.\\\" Although stratification of the risk for treatment resistance and toxicity is key to precision oncology, there are multiple ways in which such stratification can be achieved, for example, genetic, functional pathway based, among others. Moving toward precision oncology is sorely needed in the case of acute lymphoblastic leukemia (ALL) wherein adult patients display survival rates ranging from 30% to 70%. The present study reports on the pathway activity signature of adult B-ALL, with an eye to precision oncology. Transcriptome profiles from three different expression datasets, comprising 346 patients who were adolescents or adults with B-ALL, were harnessed to determine the activity of signaling pathways commonly disrupted in B-ALL. Pathway activity analyses revealed that Ph-like ALL closely resembles Ph-positive ALL. Although this was the case at the average pathway activity level, the pathway activity patterns in B-ALL differ from genetic subtypes. Importantly, clustering analysis revealed that five distinct clusters exist in B-ALL patients based on pathway activity, with each cluster displaying a unique pattern of pathway activation. Identifying pathway-based subtypes thus appears to be crucial, considering the inherent heterogeneity among patients with the same genetic subtype. In conclusion, a pathway-based stratification of the B-ALL could potentially allow for simultaneously targeting highly active pathways within each ALL subtype, and thus might open up new avenues of innovation for personalized/precision medicine in this cancer that continues to have poor prognosis in adult patients compared with the children.</p>\",\"PeriodicalId\":2,\"journal\":{\"name\":\"ACS Applied Bio Materials\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Bio Materials\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1089/omi.2024.0145\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/19 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1089/omi.2024.0145","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/19 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
引用次数: 0
摘要
精准肿瘤学承诺为癌症患者提供量身定制的药物和临床治疗:即 "在正确的时间、以正确的剂量、为正确的患者提供正确的药物"。虽然耐药性和毒性风险分层是精准肿瘤学的关键,但实现这种分层有多种方法,例如基于基因、功能通路等。急性淋巴细胞白血病(ALL)成人患者的存活率在30%到70%之间,因此亟需向精准肿瘤学迈进。本研究报告了成人 B-ALL 的通路活性特征,着眼于精准肿瘤学。研究人员利用来自三个不同表达数据集的转录组图谱(包括346名青少年或成人B-ALL患者)来确定B-ALL中常见信号通路的活性。通路活性分析表明,Ph 样 ALL 与 Ph 阳性 ALL 非常相似。虽然在平均通路活性水平上是如此,但B-ALL的通路活性模式因基因亚型而异。重要的是,聚类分析显示,根据通路活性,B-ALL 患者中存在五个不同的群组,每个群组都显示出独特的通路激活模式。因此,考虑到同一基因亚型患者之间固有的异质性,识别基于通路的亚型似乎至关重要。总之,对B-ALL进行基于通路的分层有可能同时针对每种ALL亚型中的高活性通路,从而为这种癌症的个性化/精准医疗开辟新的创新途径,因为与儿童相比,成年患者的预后仍然较差。
Expanding Beyond Genetic Subtypes in B-Cell Acute Lymphoblastic Leukemia: A Pathway-Based Stratification of Patients for Precision Oncology.
Precision oncology promises individually tailored drugs and clinical care for patients with cancer: That is, "the right drug, for the right patient, at the right dose, and at the right time." Although stratification of the risk for treatment resistance and toxicity is key to precision oncology, there are multiple ways in which such stratification can be achieved, for example, genetic, functional pathway based, among others. Moving toward precision oncology is sorely needed in the case of acute lymphoblastic leukemia (ALL) wherein adult patients display survival rates ranging from 30% to 70%. The present study reports on the pathway activity signature of adult B-ALL, with an eye to precision oncology. Transcriptome profiles from three different expression datasets, comprising 346 patients who were adolescents or adults with B-ALL, were harnessed to determine the activity of signaling pathways commonly disrupted in B-ALL. Pathway activity analyses revealed that Ph-like ALL closely resembles Ph-positive ALL. Although this was the case at the average pathway activity level, the pathway activity patterns in B-ALL differ from genetic subtypes. Importantly, clustering analysis revealed that five distinct clusters exist in B-ALL patients based on pathway activity, with each cluster displaying a unique pattern of pathway activation. Identifying pathway-based subtypes thus appears to be crucial, considering the inherent heterogeneity among patients with the same genetic subtype. In conclusion, a pathway-based stratification of the B-ALL could potentially allow for simultaneously targeting highly active pathways within each ALL subtype, and thus might open up new avenues of innovation for personalized/precision medicine in this cancer that continues to have poor prognosis in adult patients compared with the children.