Abstract 1062: Development and characterization of patient-derived xenograft models for acute myeloid leukemia

Abstract

Abstract Drug development for acute myeloid leukemia (AML) remains challenging, in part, due to the lack of preclinical models that reflect the biology of AML patients. For example, while the majority of AML patients express both CD33 and CD123, only a small fraction of AML cell lines express CD123. Similarly, most AML cell lines have a differentiated phenotype, which may bias the evaluation towards certain types of AML. To address these challenges, we developed a dozen patient derived xenograft (PDX) models to aid preclinical development of AML drugs. Bone marrow samples from 32 AML patients were implanted intravenously into NSG mice. Thirteen of them led to successful expansion of human CD45+ cells in the bone marrow, as demonstrated by flow cytometry. Twelve of these established disease in a secondary passage. Using multicolor flow cytometry analysis, we found that expression of CD33 and CD123 were preserved from AML patients and engrafted disease in NSG mice. Moreover, RNA-sequencing analysis demonstrated that gene expression largely remained consistent between the first two passages. Detailed genetic analysis demonstrated the preservation AML-relevant mutations, such as FLT3-ITD mutations and IDH2 mutations in the PDX model. In summary, we have successfully established AML PDX models that reflect the antigen expression and molecular genetics of AML patients. These models may facilitate the future development of antibody-based therapeutics. Citation Format: Michelle Ulrich, Martha Anderson, Robert Thurman, Fu Li. Development and characterization of patient-derived xenograft models for acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1062.