Comprehensive characterization of patient-derived xenograft models of pediatric leukemia

Anna Rogojina, Laura J. Klesse, Erin Butler, Jiwoong Kim, He Zhang, Xue Xiao, Lei Guo, Qinbo Zhou, Taylor Hartshorne, Dawn Garcia, Korri Weldon, Trevor Holland, Abhik Bandyopadhyay, Luz Perez Prado, Shidan Wang, Donghan M. Yang, Anne Marie Langevan, Yi Zou, Allison C. Grimes, Chatchawin AssanasenVinod Gidvani-Diaz, Siyuan Zheng, Zhao Lai, Yidong Chen, Yang Xie, Gail E. Tomlinson, Stephen X. Skapek, Raushan T. Kurmasheva, Peter J. Houghton, Lin Xu

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Patient-derived xenografts (PDX) remain valuable models for understanding the biology and for developing 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 leukemia 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 alterations, 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 childhood leukemias represents a valuable resource in that germline DNA sequencing has allowed the unambiguous determination of somatic mutations in both PT and PDX.

Original languageEnglish (US)
Article number108171
JournaliScience
Volume26
Issue number11
DOIs
StatePublished - Nov 17 2023

Keywords

  • Cancer
  • Omics
  • Transcriptomics

ASJC Scopus subject areas

  • General

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