iScience (Nov 2023)
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 Assanasen,
- Vinod Gidvani-Diaz,
- Siyuan Zheng,
- Zhao Lai,
- Yidong Chen,
- Yang Xie,
- Gail E. Tomlinson,
- Stephen X. Skapek,
- Raushan T. Kurmasheva,
- Peter J. Houghton,
- Lin Xu
Affiliations
- Anna Rogojina
- Greehey Children’s Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA
- Laura J. Klesse
- Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; Gill Center for Cancer and Blood Disorders, Children’s Health Children’s Medical Center, Dallas, TX, USA
- Erin Butler
- Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; Gill Center for Cancer and Blood Disorders, Children’s Health Children’s Medical Center, Dallas, TX, USA
- Jiwoong Kim
- Quantitative Biomedical Research Center, Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA
- He Zhang
- Quantitative Biomedical Research Center, Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Xue Xiao
- Quantitative Biomedical Research Center, Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Lei Guo
- Quantitative Biomedical Research Center, Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Qinbo Zhou
- Quantitative Biomedical Research Center, Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Taylor Hartshorne
- Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Dawn Garcia
- Greehey Children’s Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA
- Korri Weldon
- Greehey Children’s Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA
- Trevor Holland
- Greehey Children’s Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA
- Abhik Bandyopadhyay
- Greehey Children’s Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA
- Luz Perez Prado
- Greehey Children’s Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA
- Shidan Wang
- Quantitative Biomedical Research Center, Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Donghan M. Yang
- Quantitative Biomedical Research Center, Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Anne-Marie Langevan
- Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Texas Health San Antonio, San Antonio, TX, USA; Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA
- Yi Zou
- Greehey Children’s Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA
- Allison C. Grimes
- Greehey Children’s Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA; Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Texas Health San Antonio, San Antonio, TX, USA; Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA
- Chatchawin Assanasen
- Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Texas Health San Antonio, San Antonio, TX, USA
- Vinod Gidvani-Diaz
- Methodist Children’s Hospital, San Antonio, TX, USA
- Siyuan Zheng
- Greehey Children’s Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA; Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA; Department of Population Health Sciences, University of Texas Health San Antonio, San Antonio, TX, USA
- Zhao Lai
- Greehey Children’s Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA; Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA; Department of Molecular Medicine, University of Texas Health San Antonio, San Antonio, TX, USA
- Yidong Chen
- Greehey Children’s Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA; Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA; Department of Population Health Sciences, University of Texas Health San Antonio, San Antonio, TX, USA
- Yang Xie
- Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; Quantitative Biomedical Research Center, Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Bioinformatics, University of Texas Southwestern Medical Center, Dallas, TX, USA
- Gail E. Tomlinson
- Greehey Children’s Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA; Department of Pediatrics, Division of Pediatric Hematology Oncology, University of Texas Health San Antonio, San Antonio, TX, USA; Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA
- Stephen X. Skapek
- Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX, USA; Gill Center for Cancer and Blood Disorders, Children’s Health Children’s Medical Center, Dallas, TX, USA; Corresponding author
- Raushan T. Kurmasheva
- Greehey Children’s Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA; Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA
- Peter J. Houghton
- Greehey Children’s Cancer Research Institute, University of Texas Health San Antonio, San Antonio, TX, USA; Mays Cancer Center, University of Texas Health San Antonio, San Antonio, TX, USA; Corresponding author
- Lin Xu
- Department of Pediatrics, Division of Hematology/Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA; Quantitative Biomedical Research Center, Peter O’Donnell Jr. School of Public Health, University of Texas Southwestern Medical Center, Dallas, TX, USA; Corresponding author
- Journal volume & issue
-
Vol. 26,
no. 11
p. 108171
Abstract
Summary: 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.
