Acute lymphoblastic leukemia (ALL) is a malignant hematologic tumor with highly aggressive characteristics, which has 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. 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 to assess the potential ADR they may have on healthy organs. In this article we briefly introduce the clinical status of ALL, review ALL animal models’ progression, their roles in revealing the pathogenesis of ALL and drug development.

Background and Purpose Neutrophils and the release of neutrophil extracellular traps (NETs) play important roles in the pathogenesis of RA. However, IgD, which was abnormally higher in RA, has not been studied for its pathological role in neutrophil activation and NETs formation. Experimental Approach Peripheral blood of RA patients and healthy controls were collected and adjuvant-induced arthritis (AA) rat models were established. Body weights, the severity of arthritis of AA rats were monitored regularly. After being stimulated with IgD, expression of FcδR on neutrophils and NETs formation were analyzed with multiple approaches such as flow cytometry, scanning electron microscopy, western blot, and qPCR. IgD-Fc-Ig were used to block interactions between IgD-FcδR. Additionally, the effect of IgD-induced neutrophils or NETs on FLS was assayed. Key Results As a specific marker of NETs, the level of citrullinated histone H3 was positively correlated with sIgD and FcδR in RA patients. IgD enhances the release of NETs by activating neutrophils. IgD-Fc-Ig could significantly reduce NETs formation and FcδR expression on neutrophils in vitro. In vivo, IgD-Fc-Ig treatment significantly regulates the neutrophil activity and NETs formation. IgD-Fc-Ig could restrain IgD-induced neutrophil activation and NETs formation, thus inhibiting FLS proliferation. Conclusions and Implications Neutrophils were activated by IgD, which suggests that neutrophils play a role in inducing FLS proliferation in RA patients who have abnormally higher IgD levels, there by increasing the severity of the disease. Blocking FcδR inhibited neutrophil activation and may represent an additional attractive novel therapeutic strategy for the treatment of RA.