Comprehensive characterization of patient-derived xenograft models of pediatric leukemia

Patient-derived xenografts (PDX) remain valuable models for understanding the biology and for devel-oping novel therapeutics. To expand current PDX models of childhood leukemia, we have developed new PDX models from Hispanic patients, a subgroup with a poorer overall outcome. Of 117 primary leu-kemia samples obtained, successful engraftment and serial passage in mice were achieved in 82 samples (70%). Hispanic patient samples engrafted at a rate (51/73, 70%) that was similar to non-Hispanic patient samples (31/45, 70%). With a new algorithm to remove mouse contamination in multi-omics datasets including methylation data, we found PDX models faithfully reflected somatic mutations, copy-number al-terations, RNA expression, gene fusions, whole-genome methylation patterns, and immunophenotypes found in primary tumor (PT) samples in the first 50 reported here. This cohort of characterized PDX child-hood leukemias represents a valuable resource in that germline DNA sequencing has allowed the unam-biguous determination of somatic mutations in both PT and PDX.

Automated summary

Patient-derived xenografts (PDX) are valuable tools for studying biology and developing new therapies. In this study, researchers successfully developed PDX models from Hispanic childhood leukemia patients and found that these models accurately reflected the genetic abnormalities and expression patterns found in the primary tumors.