Animal models of acute lymphoblastic leukemia: Recapitulating the human disease to evaluate drug efficacy and discover therapeutic targets

Acute lymphoblastic leukemia (ALL) is a malignant hematologic tumor with highly aggressive characteristics, which is prone to relapse, has a poor prognosis and few clinically effective drugs. It is meaningful to gain a better understanding of its pathogenesis in order to discover and evaluate potential therapeutic drugs and new treatment targets. The goal of developing novel targeted drugs and treatment methods is to increase complete remission, reduce toxicity and morbidity, and that is also the most important prerequisite for modern leukemia treatment. However, the process of new drugs from research and development to clinical application is long and difficult. Many promising drugs were rejected by the US Food and Drug Administration (FDA) due to serious adverse drug reactions (ADR) in clinical phase I trials. Animal models provide us with an excellent tool to understand the complex pathological mechanisms of human diseases, to evaluate the potential of new targeted drugs and therapeutic approaches to treat ALL in vivo and, more importantly, to assess the potential ADR they may have on healthy organs. In this article we review ALL animal models' progression, their roles in revealing the pathogenesis of ALL and drug development. Additionally, we mainly focus on the mouse models, especially xenotransplantation and transgenic models that more closely reproduce the human phenotype. In conclusion, we summarize the advantages and limitations of each model, thereby facilitating further understanding the etiology of ALL, and eventually contributing to the effective management of the disease.