{"title":"急性髓性白血病中的 BCL-2 抑制剂：抗药性与联合用药。","authors":"Qi Zhang Tatarata, Zhe Wang, Marina Konopleva","doi":"10.1080/17474086.2024.2429604","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>The introduction of venetoclax has revolutionized the treatment landscape of acute myeloid leukemia, offering new therapeutic opportunities. However, the clinical response to venetoclax varies significantly between patients, with many experiencing limited duration of response.</p><p><strong>Areas covered: </strong>Identified resistance mechanisms include both intrinsic and acquired resistance to VEN. The former is associated with cell lineage and differentiation state. The latter includes dependency on alternative BCL-2 family anti-apoptotic protein(s) mediated by genetic, epigenetic, or post-translational mechanisms, mitochondrial and metabolic involvement, as well as microenvironment. Understanding these mechanisms is crucial for optimizing venetoclax-based therapies and enhancing treatment outcomes for patients with acute myeloid leukemia. This review aims to elucidate the primary mechanisms underlying resistance to venetoclax and explore current therapeutic strategies to overcome this challenge.</p><p><strong>Expert opinion: </strong>In patients with venetoclax resistance, alternative options include targeted combination therapies tailored to individual cases based on cytogenetics and prior treatments. Many of these therapies require further clinical investigation to validate their safety and efficacy.</p>","PeriodicalId":12325,"journal":{"name":"Expert Review of Hematology","volume":" ","pages":"1-12"},"PeriodicalIF":2.3000,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"BCL-2 inhibition in acute myeloid leukemia: resistance and combinations.\",\"authors\":\"Qi Zhang Tatarata, Zhe Wang, Marina Konopleva\",\"doi\":\"10.1080/17474086.2024.2429604\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>The introduction of venetoclax has revolutionized the treatment landscape of acute myeloid leukemia, offering new therapeutic opportunities. However, the clinical response to venetoclax varies significantly between patients, with many experiencing limited duration of response.</p><p><strong>Areas covered: </strong>Identified resistance mechanisms include both intrinsic and acquired resistance to VEN. The former is associated with cell lineage and differentiation state. The latter includes dependency on alternative BCL-2 family anti-apoptotic protein(s) mediated by genetic, epigenetic, or post-translational mechanisms, mitochondrial and metabolic involvement, as well as microenvironment. Understanding these mechanisms is crucial for optimizing venetoclax-based therapies and enhancing treatment outcomes for patients with acute myeloid leukemia. This review aims to elucidate the primary mechanisms underlying resistance to venetoclax and explore current therapeutic strategies to overcome this challenge.</p><p><strong>Expert opinion: </strong>In patients with venetoclax resistance, alternative options include targeted combination therapies tailored to individual cases based on cytogenetics and prior treatments. Many of these therapies require further clinical investigation to validate their safety and efficacy.</p>\",\"PeriodicalId\":12325,\"journal\":{\"name\":\"Expert Review of Hematology\",\"volume\":\" \",\"pages\":\"1-12\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2024-11-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Expert Review of Hematology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1080/17474086.2024.2429604\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Expert Review of Hematology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/17474086.2024.2429604","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"HEMATOLOGY","Score":null,"Total":0}
BCL-2 inhibition in acute myeloid leukemia: resistance and combinations.
Introduction: The introduction of venetoclax has revolutionized the treatment landscape of acute myeloid leukemia, offering new therapeutic opportunities. However, the clinical response to venetoclax varies significantly between patients, with many experiencing limited duration of response.
Areas covered: Identified resistance mechanisms include both intrinsic and acquired resistance to VEN. The former is associated with cell lineage and differentiation state. The latter includes dependency on alternative BCL-2 family anti-apoptotic protein(s) mediated by genetic, epigenetic, or post-translational mechanisms, mitochondrial and metabolic involvement, as well as microenvironment. Understanding these mechanisms is crucial for optimizing venetoclax-based therapies and enhancing treatment outcomes for patients with acute myeloid leukemia. This review aims to elucidate the primary mechanisms underlying resistance to venetoclax and explore current therapeutic strategies to overcome this challenge.
Expert opinion: In patients with venetoclax resistance, alternative options include targeted combination therapies tailored to individual cases based on cytogenetics and prior treatments. Many of these therapies require further clinical investigation to validate their safety and efficacy.
期刊介绍：
Advanced molecular research techniques have transformed hematology in recent years. With improved understanding of hematologic diseases, we now have the opportunity to research and evaluate new biological therapies, new drugs and drug combinations, new treatment schedules and novel approaches including stem cell transplantation. We can also expect proteomics, molecular genetics and biomarker research to facilitate new diagnostic approaches and the identification of appropriate therapies. Further advances in our knowledge regarding the formation and function of blood cells and blood-forming tissues should ensue, and it will be a major challenge for hematologists to adopt these new paradigms and develop integrated strategies to define the best possible patient care. Expert Review of Hematology (1747-4086) puts these advances in context and explores how they will translate directly into clinical practice.
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