Zebrafish models of human leukemia: technological advances and mechanistic insights

Abstract

Improved therapeutic strategies for patients with leukemia remain in great demand and beckon better understanding of the mechanisms underlying leukemic treatment resistance and relapse. Accordingly, discoveries in leukemic pathophysiology have been achieved in various animal models. Danio rerio—commonly known as the zebrafish—is a vertebrate organism well suited for the investigation of human leukemia. Zebrafish have a conserved hematopoietic program and unique experimental strengths. Recent technological advances in zebrafish research including efficient transgenesis, precise genome editing, and straightforward transplantation techniques have led to the generation of numerous zebrafish leukemia models. Additionally, improved imaging techniques, combined with the transparency of zebrafish, have revealed exquisite details of leukemic initiation, progression, and regression. Finally, advances in high-throughput drug screening in zebrafish are likely to hasten the discovery of novel anti-leukemic agents. Zebrafish provide a reliable experimental system for leukemic disease research and one in which investigators have accumulated knowledge concerning the genetic underpinnings of leukemic transformation and treatment resistance. Without doubt, zebrafish are rapidly expanding our understanding of disease mechanism and are helping to shape therapeutic strategy for improved patient outcomes.