Advances and challenges in zebrafish models of T-cell acute lymphoblastic leukemia

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) presents a significant challenge in oncology, necessitating innovative research approaches for improved comprehension and therapeutic advancements. In recent years, zebrafish (Danio rerio) have emerged as a vital model organism in T-ALL research, conferring distinctive advantages over conventional models. Zebrafish, sharing substantial genetic homology with humans, accurately replicate key phenotypic and molecular features of human T-ALL, including clonal expansion, aneuploidy, organ infiltration, and gene expression profiles. They also develop chromosomal translocations similar to those in human T-ALL. This comprehensive review explores the diverse zebrafish T-ALL models, encompassing genetic alterations and inducible systems that facilitate the investigation of disease initiation, progression, and response to therapy. These models have revealed critical insights into the roles of specific genes and the identification of novel oncogenic drivers. Moreover, zebrafish models enable high-throughput drug screening, providing an expedited path toward discovering potential therapeutics. However, while zebrafish models present exceptional advantages, they are not without challenges, including genetic differences, biological disparities, and technical complexities. To exploit the potential of zebrafish in T-ALL research, ongoing efforts are directed toward CRISPR/Cas9 gene editing, improved antibody development, and enhanced experimental techniques.