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.