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Updated: Jul 14, 2026
Pre-clinical Evaluation of Tyrosine Kinase Inhibitors for Treatment of Acute Leukemia
Published on: September 18, 2013
In vivo models of childhood leukemia for preclinical drug testing
Petra S Bachmann1, Richard B Lock
1Children's Cancer Institute Australia for Medical Research, University of New South Wales, Sydney, Australia. rlock@ccia.unsw.edu.au
Abstract:
The number of new anti-cancer drugs emerging for clinical trials in humans far exceeds the availability of pediatric acute leukemia patients to be entered into clinical trials. Therefore, preclinical testing of new agents for the treatment of childhood acute leukemia is essential to ensure that the most promising drugs are prioritized to enter clinical trials. Historically, the murine system has been central to modeling human leukemia in vivo. A greater knowledge of the molecular lesions underlying particular subtypes of leukemia has led to the generation of genetically engineered murine models, generally involving the knockin or knockout of certain genes and fusion genes at their normal genetic locus. However, the most predominant in vivo models for preclinical drug testing have been human leukemia xenografts. Successful engraftment of all subtypes of acute lymphoblastic leukemia, most subtypes of acute myeloid leukemia as well as juvenile myelomonocytic leukemia, chronic myeloid leukemia and chronic lymphocytic leukemia have been described in various immune-deficient murine hosts. Preclinical testing of novel therapeutics in vivo will likely identify the most promising new agents to enter clinical trials, and will allow their future use to be optimized in combination with other novel and conventional chemotherapeutics.
Insights
Preclinical testing of novel anti-cancer drugs in animal models is crucial for prioritizing effective treatments for childhood acute leukemia. In vivo models, particularly human leukemia xenografts, are vital for evaluating new therapeutic agents.
Area of Science:
- Hematology and Oncology
- Translational Medicine
- Pharmacology
Background:
- The pipeline of new anti-cancer drugs for clinical trials outpaces the availability of pediatric acute leukemia patients for enrollment.
- Effective preclinical testing is essential to identify and prioritize the most promising agents for childhood leukemia treatment.
Purpose of the Study:
- To highlight the importance of preclinical testing for novel anti-cancer drugs in childhood acute leukemia.
- To review the utility of established in vivo models for evaluating therapeutic efficacy.
Main Methods:
- Review of historical and current in vivo models for leukemia research, including genetically engineered murine models.
- Focus on human leukemia xenografts in immune-deficient murine hosts as a predominant preclinical testing platform.
- Discussion of successful engraftment across various leukemia subtypes (ALL, AML, JMML, CML, CLL).
Main Results:
- Human leukemia xenografts have demonstrated successful engraftment across a wide spectrum of acute and chronic leukemia subtypes in immune-deficient mice.
- These models provide a viable system for the preclinical evaluation of novel therapeutic agents.
Conclusions:
- In vivo preclinical testing is indispensable for identifying promising novel therapeutics for childhood acute leukemia.
- Optimizing the use of these agents in combination with existing and new chemotherapeutics is facilitated by robust preclinical data.
