Project Term
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Project Summary
Pediatric AML is a disease with poor outcomes and a need for improved therapeutic options. Pediatric AML is characterized by diverse lesions that often do not overlap with adult AML, which therefore means therapeutic development must be done using pediatric AML models. Recent advances in patient derived xenograft (PDX) modeling have made possible the successful development of PDX models of diverse pediatric AML subtypes.
Lay Abstract
Pediatric AML is a disease with poor outcomes and a need for improved therapeutic options. Pediatric AML is characterized by diverse genetic changes driving the leukemia that often do not overlap with adult AML. These differences therefore mean that development and testing of novel targeted therapies and studies into understanding the biology of pediatric AML must be done using pediatric AML specific models. Recent advances in patient-derived xenograft (PDX) modeling have made possible the successful development of PDX models for many types of adult cancers. However, development of PDX models is very time consuming and expensive which has resulted in very few established pediatric AML PDX models – which has created a barrier for efficient preclinical testing.
Our laboratory at Texas Children’s Hospital (TCH) has a very close connection to our large inpatient and outpatient pediatric oncology clinical service. Each year, TCH sees 15-25 patients with newly diagnosed pediatric AML and 5-15 patients with relapsed pediatric AML. This volume is one of the largest in the country as only 500 cases of pediatric AML are diagnosed in the US annually. All newly diagnosed patients undergo extensive genetic testing of their leukemia and most approached patients/families consent to the use of leukemia samples for local research efforts towards improving outcomes for pediatric AML. In addition, our laboratory routinely receives frozen pediatric AML samples collected through the Children’s Oncology Group from patients and families across the world who have consented to provide samples for research. Utilizing these two sources of pediatric AML leukemia samples and with the support of Blood Cancer United and several family foundations we have taken a grassroots effort to develop pediatric AML PDX models with the goal of making these freely available to researchers working to improve outcomes for pediatric AML. All our patient samples have detailed clinical information available for reference. These characteristics of our PDX repository provide a rich resource for preclinical testing of new therapies for pediatric AML. Funding from Blood Cancer United supports the infrastructure of the PDX program allowing us to continue to fill this important gap in pre-clinical testing for children with AML.
Program
