Qin Ronghao, Liang Yuxing, Zhou Fuling
Department of Hematology, Zhongnan Hospital of Wuhan University, Wuhan 430072, Hubei, China.
Cancer Drug Resist. 2025 May 28;8:23. doi: 10.20517/cdr.2025.18. eCollection 2025.
Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) are genetically heterogeneous malignancies of hematopoietic stem cells, characterized by complex mutations and a high risk of drug resistance and relapse. Patient-derived xenograft (PDX) models are dynamic entities transplanted with leukemia stem cells (LSCs), retaining patients' biological and genetic characteristics. By elucidating LSCs, clonal dynamics, and microenvironment interaction, PDXs facilitate the preclinical evaluation of therapy sensitivity, including immunotherapies, epigenetic therapies, and other agents targeting mutated proteins or apoptosis. The application of PDXs has provided translational evidence for various studies with reliable clinical relevance. Additionally, conventional PDXs remain a robust tool in identifying drug resistance compared with other models, and their potential is further unleashed when examined in large cohorts or combined with novel technologies, which not only enhances our understanding of acute leukemia biology but also enables the discovery and identification of novel biomarkers. In this review, we present the application of PDX models for acute leukemia resistance, including mechanism investigation, therapy evaluation, and associated challenges.
急性髓系白血病（AML）和急性淋巴细胞白血病（ALL）是造血干细胞的基因异质性恶性肿瘤，其特征为复杂突变以及耐药和复发风险高。患者来源的异种移植（PDX）模型是移植了白血病干细胞（LSC）的动态实体，保留了患者的生物学和遗传学特征。通过阐明LSC、克隆动力学和微环境相互作用，PDX有助于对包括免疫疗法、表观遗传疗法以及其他靶向突变蛋白或细胞凋亡的药物进行治疗敏感性的临床前评估。PDX的应用为各种具有可靠临床相关性的研究提供了转化证据。此外，与其他模型相比，传统的PDX在识别耐药性方面仍然是一个强大的工具，当在大型队列中进行研究或与新技术结合时，其潜力会得到进一步释放，这不仅增强了我们对急性白血病生物学的理解，还能发现和鉴定新的生物标志物。在本综述中，我们介绍了PDX模型在急性白血病耐药性方面的应用，包括机制研究、治疗评估及相关挑战。
